Aim of study:Diabetic kidney disease (DKD) is a serious complication of longstanding diabetes and its pathogenesis remains unclear.Longstanding hyperglycemia,along with other factors,is associated with accelerated decline of kidney function in patients with type 2 diabetic kidney disease.db/db mice,a rodent model of type 2 diabetes is intensively used to study type 2 diabetes and complications.In order to accelerate DKD pathogenesis process to carry out correlated research,we observed whether high fat diet (HFD) accelerates DKD and caused renal failure in db/db mice.Material and methods:8 weeks old db/db mice were randomly divided into a regular diet group (RD) and a high fat diet group (HFD) lasting 8 weeks,.The high fat diet consisted of 24% protein,41.0% carbohydrate,24.0% fat.During the experimental session,bodyweight gain,food-intake and water-intake were assayed every week or every day.Plasm levels of glucose,triglyceride,total cholesterol,free fatty acid,HDL-C,LDL-C,insulin,creatinine and urea nitrogen were determined using enzyme-linked immunosorbent assay.The blood pressure,24h-urine output and 24h-urine protein were determined at the eighth week.At the end of study,the mice were sacrificed and calculated kidney organ index,renal histopathology was evaluated under light microscopy Results:Our results indicated that HFD dramatically increased the db/db mice plasm levels of glucose,triglyceride,total cholesterol,free fatty acid,HDL-C,LDL-C,insulin,creatinine and urea nitrogen,elevated the HOMA-IR index.The blood pressure,24 h-urine output and 24h-urine protein were observed significant increase in HFD-fed db/db mice as compared with RD-fed db/db mice.HFD aggravated the pathological morphology change of mouse kidney while kidney organ index no significant changes.In addition to,we also found persistent HFD feeding resulted in early death of db/db mice,which was associated with oliguria and anuria,also with plasm insulin level dramatically descend.Conclusions:Our results suggest that HFD may worsen diabetic nephropathy and cause renal failure by exacerbating the metabolic abnormality in db/db mice.