Lead is a pervasive environmental toxin that affects multiple organ systems, including the nervous, renal, reproductive and hematological systems. Even though lead is probably the most studied toxic metal, some of the symptoms of lead toxicity still cannot be explained by the known molecular mechanisms. Therefore, lead induced oxidative stress has recently started to gain attention. This experimental study is planned to investigate the- role of oxidative stress as a possible mechanism of sub-chronic lead induced neuro- toxicity in rats and to evaluate the role of alphatocopherol (Vitamin E) as anti oxidant in reversing this effect. In order to achieve our goal, we measured both the blood level. Morever, the enzyme activities of reduced glutathione (GSH ), glutathioneperoxidase (GPx), superoxide dismutase (SOD),malondialdhyde (MDA), 8-hydrodydeoxyguanosine (8-OHDG) were determinedin brain tissues of lead acetate exposed rats in the presence or absence of Vit. E. Increases in MDA, 8- OHDG contents were observed in brain's of rats received only lead acetate but supplementation with Vit. E returned these measures to nearly pretreatrnent levels. The level of GSH, SOD and GPx. significantly decreased in lead acetate exposed rats but increased to about pre- treatment levels in supplementation of Vit.E concomitantly to lead acetate treated rats. This study also showed that administration of lead acetate to male rats had elevated blood and brain lead level which not decreased on administration of Vit. E concomitantly. To confirm these results a histopathological examination of rats brain were done. Histopathological changes were observed in the brain of lead exposed rats in the form of sever edema, gliosis, and neuronal degeneration, but addition of Vit. E concomitantly to lead showed mild changes in the form of mild edema, and gliosis. These results suggests that Vit.E can protect against oxidative stress effect of lead inducing neurotoxicity by its antioxidant effect, but not associated with decreasing brain or blood lead level.