Background: Nitric oxide (NO), a major chemical form of endothelium-derived relaxing factor and an important regulator of vascular tone, is released by endothelial cells. The role of NO is not restricted to the vascular system, and it participates in the regulation of renal hemodynamics and renal excretory function. There are increasing evidences indicating that the elevated levels of NO play a primary pathogenic role in the glomerular injury and renal failure. Objectives: We sought to investigate the renoprotective or nephrotoxic effects of various doses of isosorbide dinitrate as an exogenous model, and induction of cholestasis as an endogenous model of NO overproduction on renal function and structure. Methods: Parameters such as plasma and urine p-nitrophenyl-N-acetyl-β-D-glucosaminidase (NAG)-activity, urea and creatinine levels were measured. Results: Urea, creatinine and NAG-activity in rats treated by different doses of isosorbide as well as in cholestasis induced rats, were higher than control group. This elevation was significantly pronounced at higher doses of isosorbide. Conclusion: NO overproduction would be nephrotoxic due to oxidizing products of NO, peroxynitrite anion (ONOO–), formed by the reaction of NO and superoxide radical (O2–).