Abstract: Objective To assess the renal protective effects of mycophenolate mofetil(MMF) in diabetic model rats and explore its mechanism. Methods SD rats were divided randomly into there groups: control group,diabetic model group and diabetic group treated with MMF. Observed twelve weeks, blood glucose(BG), blood urea nitrogen(BUN), serum creatinine(Scr), index number of kidney hypertrophy(kidey weight to body weight, KW/BW),creatinine clearance(Ccr) and 24- hour urinary protein (24Upro) were detected. Kidney tissure were examined by light microscopy and electron microscopy. The protein exprssion of intercellular adhesion molecule-1 (ICAM-1) and proliferating cell nuclear antigen(PCNA) in kidney tissure were determined by immunohistochemical technique. The mRNA expression of ICAM-1 in kidney tissure were semi-quantitatively determined with reverse transcription-polymerase chain reaction(RT--PCR). Results Compared with control group, BG ﹑KW/BW﹑24Upro﹑BUN﹑Scr and Ccr were significantly increased in diabetic model rats(P<0.05 or 0.01), the density of mesangium and the depth of glomerular basement membrane were significantly enlarged(P<0.01), the protein expression of ICAM-1 and PCNA and the mRNA expression of ICAM-1 were significantly up-regulated (P<0.05or 0.01). Except blood glucose, the above mentioned parameters in MMF treated group were all significantly inhibited(P<0.05 or 0.01). Conclusion MMF showed the protective effect for diabetic nephropathy. The mechanism may be correlated with that it down-regulate the exprssion of ICAM-1 and PCNA.