Background and Objectives: Diabetic nephropathy (DN) is the leading cause of end stage renal disease. The aim of this
study is to demonstrate the possible mechanism of reno-protective role of Simvastatin (SMV), a lipophilic compound
against streptozotocin induced diabetic nephropathy.Methods and Results: Thirty-five adult male albino rats were divided into control group, diabetes group and SMV treated diabetic group 40 mg/Kg/ day for 8 weeks. Animals were sacrificed and the kidneys were dissected out and prepared to be stained with hematoxylin and eosin, periodic acid sheif (PAS), toluidine blue and immunohistochemical staining against inducible nitric oxide synthase (iNOS). Ultrathin sections were also prepared. Morphometric measurements and statistical analysis were done. Diabetic group revealed glomerular and tubular affection in addition to significantly increased PAS staining and immunostaining of iNOS. Electron microscopy revealed affected glomerular basement membrane,endothelium and podocyte. Treatment with SMV markedly attenuated these changes with significant decrease in PAS stain and iNOS immunostain. Conclusion: Simvastatin could attenuate streptozotocin induced DN through many factors as lipo-protection, antiinflammatory and antioxidant effects. This anti-inflammatory and antioxidant effects could be through inhibition of iNOS enzyme and secondary decreased production of NO.