Type I diabetes is the result of autoimmune destruction of the pancreatic islets. Islet infiltrating macrophages, upon activation, would produce reactive oxygen and nitrogen free radicals and these reactive intermediates could be directly toxic to the β-cells. Lipid peroxidation is one of the important free radical reactions and many authors suggest an association between increased lipid peroxidation and the diabetogenic process in type I diabetes.This study aims to evaluate the effect of administration vitamin E, L-arginine, and Nω-nitro-L-arginine methyl ester (L-NAME), on the onset and severity of streptozotocin-induced diabetes in rats (an experimental model of type I diabetes). In this study, preventive dose of vitamin E 200mg/kg/day orally for 3 weeks significantly prevented the rise in blood glucose level without complete protection against development of type I diabetes. Also, vitamin E prevented the rise in the level of pancreatic tissue malondialdehyde denoting complete protection against lipid peroxidation. Streptozotocin produced mild destructive changes in the pancreatic beta-cells following vitamin E administration. As regard L-arginine (NO donor), 300mg/kg/day orally for 3 weeks, preventive dose was not protective against type I diabetes as evident by non significant changes in the levels of blood glucose and pancreatic tissue malondialdehyde inspite of moderate pancreatic beta-cell destruction. L-NAME 27mg/kg/day orally for 3weeks before streptozotocin administration, significantly prevented the rise in blood glucose level with mild.