Background Podocyte has inflammatory role in the development of diabetic nephropathy (DN).Mycophenolate mofetil(MMF),an anti-inflammatory agent,can suppress macrophage infiltration and reduce renal injury instreptozotocin-induced diabetic rats.Angiotensin Ⅱ receptor blocker (ARB),another renal protecting agent,can decreasepodocyte loss in DN.In this study,we detected the expression levels of monocyte chemoattractant protein-1 (MCP-1) andnephrin to evaluate podocyte’s role in inflammatory reaction in DN,observe and compare the effect of MMF alone and incombination with valsartan,on preventing podocyte loss in streptozotocin (STZ) induced diabetic rats.Methods Diabetic model was constructed in uninephrectomized male Wistar rats by single peritoneal injection of STZ(65 mg/kg).The successfully induced diabetic rats were randomly divided into four groups:diabetes without treatmentgroup (DM),valsartan treated group (DMV),MMF treated group (DMM),and combined therapy group (DMVM).Normalrats of the same sibling were chosen as control (NC).At the end of the 8th week,serum biochemistry,24-hour urinaryprotein (UP) and the ratio of kidney weight/body weight (RWK/B) were measured.The rats were sacrificed for theobservation of renal histomorphology through light and electron microscope.Nephrin,desmin and MCP-1 levels weredetected by semi-quantitative immunohistochemical assays.Real-time quantitative PCR was used to detect the mRNAlevels of nephrin and MCP-1.Results Compared with group NC,serum glucose level,24-hour UP and RWK/B in group DM were significantly higher(P<0.01),and the nephrin mRNA level in DM group was significantly lower (P<0.05).The nephrin mRNA expressionlevels in group DMV,DMM and DMVM were all higher than that of DM group (P<0.05) and no significant differences werefound among the three treatment groups (P>0.05).Treatment with MMF,valsartan or their combination could significantlydecrease the 24-hour UP and RWK/B,and suppress glomerulosclerosis and interstitial fibrotic lesions in diabetic rats.Indiabetic rats,the high expressions of desmin and MCP-1 in kidney were suppressed by valsartan,MMF or theircombination.Conclusions Podocytes are involved in the inflammatory reaction of diabetic rats.MMF could suppress MCP-1 anddesmin expression,enhance nephrin expression,and attenuate proteinuria in diabetic rats.The combined therapy ofvalsartan and MMF did not show any superiority over monotherapies on renal protection.MMF may have renoprotectiveeffect in early stages of diabetic nephropathy through preventing podocytes loss and anti-inflammatory activity. Background Podocyte has inflammatory role in the development of diabetic nephropathy (DN). Mycophenolate mofetil (MMF), an anti-inflammatory agent, can suppress macrophage infiltration and reduce renal injury instreptozotocin-induced diabetic rats. Angiotensin II receptor blocker (ARB), another renal protecting agent, can decreasepodocyte loss in DN. this study, we detected the expression levels of monocyte chemoattractant protein-1 (MCP-1) andnephrin to evaluate podocyte’s role in inflammatory reaction in DN, observe and compare the effect of MMF alone and incombination with valsartan, on preventing podocyte loss in streptozotocin (STZ) induced diabetic rats. Methods Diabetic model was constructed in uninephrectomized male Wistar rats by single peritoneal injection of STZ (65 mg / kg). The successfully induced diabetic rats were randomly divided into four groups: diabetes without treatment group (DM), valsartan treated group (DMV), MMF treated group (DMM), and combined therapy group (DMVM) of the same sibling were chosen as control (NC) .A the end of the 8th week, serum biochemistry, 24-hour urinary protein (UP) and the ratio of kidney weight / body weight (RWK / B) were measured.The rats were sacrificed for theobservation of renal histomorphology through light and electron microscope. Nephrin, desmin and MCP-1 levels weredetected by semi-quantitative immunohistochemical assays.Real-time quantitative PCR was used to detect the mRNAsvels of nephrin and MCP-1.Results Compared with group NC, serum glucose level, 24-hour UP and RWK / B in group DM were significantly higher (P <0.01), and the nephrin mRNA level in DM group was significantly lower , DMM and DMVM were all higher than that of DM group (P <0.05) and no significant differences were found among the three treatment groups (P> 0.05). Treatment with MMF, valsartan or their combination could significantly decrease the 24-hour UP and RWK / B, and suppress glomerulosclerosis and interstitialfibrotic lesions in diabetic rats. In high glucose of desmin and MCP-1 in kidney were suppressed by valsartan, MMF or theircombination. Conclusions Podocytes are involved in the inflammatory reaction of diabetic rats. MMF could suppress MCP-1 anddesmin expression, enhance nephrin expression, and attenuate proteinuria in diabetic mice. The combined therapy ofvalsartan and MMF did not show any superiority over monotherapies on renal protection. MMF may have renoprotective effect in early stages of diabetic nephropathy through preventing podocytes loss and anti-inflammatory activity.