This study was aimed to evaluate the effect of alcoholic orange peel extract (OPE) on streptozotocin-induced diabetic nephropathy. Four weeks after the induction of diabetes, treatment with OPE (100 and 200 mg/kg) was further given for 4 weeks. Treatment with OPE 200 improved renal functions and significantly prevented the increase in creatinine, urea and blood urea nitrogen levels. Histological analysis of the kidneys revealed that tubulointerstitial fibrosis index was significantly decreased in OPE 200-treated group. The results indicated the prevention of diabetic nephropathy in rats by OPE treatment and suggest OPE as a potential treatment option.