Diabetic nephropathy presents an increasing trend worldwide. It has been an attractive area to find novel targets for the treatment of diabetic nephropathy. SIRT1 (Sirtuin 1), a member of deacetylation enzymes, regulates cell senescence, metabolism, and apoptosis. In last ten years, lots of studies showed that SIRT1 exerts a protective effect in the progression of the diabetic nephropathy by promoting reconstruction of energy homeostasis, modulating cell redox state, resisting cell apoptosis, inhibiting inflammation and ameliorating renal fibrosis. SIRT1 has become a potential new target for the treatment of diabetic nephropathy.