Abstract Background: Diabetic nephropathy (DN) has been recog-nized as the leading cause of end-stage renal disease. Resver-atrol, a polyphenolic compound, has potential role in diabetes mellitus patients. Caloric restriction (CR) has been shown to reduce the incidence diabetes mellitus (DM) complications. Aim of Study: This study aims to assess the protective effect of resveratrol (RSV) and short term caloric restriction (CR) on diabetic nephropathy. Material and Methods: Forty eight rats were divided into control group, diabetic group, Resveratrol group administered RSV 5mg/kg/day orally for 2 months after induction of diabetes, Diet restriction group subjected to 40% Caloric restriction (CR) for 2 months after induction of diabetes. Serum levels of (glucose, insulin, lipid profile, creatinine and urea with 24h micro albuminuria) in addition to assessment of HOMA-IR, sirtuin1 activity, adenosine monophosphate - activated protein kinase (AMPK) and superoxide dismutase (SOD) levels in the kidney with histopathological examination for kidney tissues. Results: Significant improvement in all parameters in resveratrol group and caloric restriction group compared to diabetic group. Also a Significant increase in SIRT1 activity, AMPK, SOD levels in kidney tissues in resveratrol group and caloric restriction groups compared to diabetic. Pathological examination of kidney tissues in diabetic group showed deterioration in renal tissue. In resveratrol and caloric restric-tion groups results showed normal structure of glomerular tufts with mild vascular degeneration. Regarding renal tubule there was no protonus cast in the lumen and mild thickening of the glomerular basement membrane. Conclusion: The SIRT1 activators like resveratrol and CR are of considerable value in protecting kidney from complication of diabetes.