Abstract: OBJECTIVE To observe the effects of resveratrol and SIRT1 activator SRT1720 on renal function and podocyte injury in diabetic rats, and to explore the possible mechanism of silent information regulator 2 related enzyme 1(SIRT1) activation to improve renal damage.METHODS Type 2 diabetic rat model was established by giving fat-enriched diets combined with unilateral nephrectomy and streptozotocin (STZ) intraperitoneal injection. Diabetic rats of the intervention group were treated with SRT1720 and resveratrol. Rats were sacrificed, kidneys and serum were collected to test renal function. Renal weight and renal weight/body weight were measured, fasting blood-glucose, serum creatinine, and urea nitrogen were detected by biochemical technique. The expression levels of podocyte slit diaphragm elements such as Nephrin and Podocin were detected by immunohistochemistry and reverse transcription real-time fluorescent quantitative PCR. RESULTS Compared with normal group, the unilateral kidney weight, ratio of kidney weight to body weight, fasting blood glucose, serum creatinine and urea nitrogen in the model rats increased significantly(P<0.05), while the protein and genetic expression of Nephrin and Podocin in renal cortex were decreased(P<0.05). Each detection index in resveratrol group or SRT1720 group was improved compared with model group. In specific, the ratio of kidney weight/body, fasting blood glucose, protein expression of Nephrin and Podocin, and gene expression of Nephrin were showed statistically significant difference between resveratrol group and model group(P<0.05). Besides, the fasting blood glucose, serum creatinine, and urea nitrogen and molecule expression of Nephrin and Podocin in the SRT1720 group were significantly different from those in the model group(P<0.05). CONCLUSION The SIRT1 activators including resveratrol and SRT1720, can significantly improve renal function damage and podocyte injury in diabetic nephropathy rats, which have important value and application prospect in the prevention and treatment of diabetic nepropathy.