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The effects of mycophenolic acid (MPA) on high glucose-induced expression of transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF) in mesangial cells (MC) were investigated. Rat MC were cultured in the presence of different concentrations of MPA (1.0 and 10.0 μmol/L) or MPA plus high glucose for 72 h. The expression of TGF-β and CTGF was detected by West blot. The results showed that high glucose could induce the expression of TGF-β and CTGF in MC, but MPA could inhibit this effects. MPA did not influence the expression of TGF-β and CTGF in normal glucose. It was concluded that MPA might prevent the progression of diabetic nephropathy by inhibiting the expression of TGF-β and CTGF in MC.