Objective:To investigate the effects of Resveratrol on the renal hypertrophy in early diabetic rats and the possible mechanism. Methods:A diabetic state was induced in 13 Spargue-Dawley rats by a single intraperitoneal injection of streptozotocin and then raised for 10 weeks. Six normal rats served as control (NC group). Diabetic rats were randomly divided into diabetic group (DM,n=7) and Resveratrol group (DR,n=6). Rats in DR group had been treated with Resveratrol 10 mg/(kg·d) intragastricly for 4 weeks. At the end of the experiments,the blood glucose (BG),body weight (BW),24 h urinary albumin excretion,serum creatinine of three groups were measuerd. Renal cortex was stained with hematoxylin and eosin. The expression of phosphorylation of 4E-BP1 protein was examined by immunohistochemistry. The expression of phosphorylation of S6 protein in the renal cortex was determined by Western blot. Results:The BW of rats in DM and DR groups decreased significantly,and the BG in DM and DR groups increased significantly compared with that in NC group (P < 0.01),and the BG of diabetic rats treated with Resveratrol improved compared with that in DM group (P < 0.05). Compared with normal rats,24 h urinary albumin excretion and serum creatinine significantly elevated in the DM and DR group (P < 0.01). 24 h urinary albumin excretion in DR group decreased significantly compared with that in DM group (P < 0.05). Resveratrol treatment attenuated glomerula mesangial cells hyperplasia,and reduced glomerula mesangial field enlargement and glomerula volume. The expressions of phosphorylation of 4E-BP1 and S6 protein in DM and DR groups were much higher than those in NC group (P < 0.01),but they were comparatively much lower in the DR group than those in DM group (P < 0.01). Conclusion:Resveratrol treatment can prevent the renal enlargement in early diabetic rats and thus halt the early step of the development of diabetic nephropathy. The mechanism is that Resveratrol may inhibit the phosphorylation of mTOR signal pathway downstream protein 4E-BP1 and S6.