Abstract: To examine the influence of vitamin E on oxidative stress and membrane ATPases. Present study conducted on hypercholesterolemic rats. The animals were divided into four equal groups. The control group was fed with chow pellets for 4.5 months. The other groups received high cholesterol or vitamin E or high cholesterol plus vitamin E. The high cholesterol and high cholesterol plus vitamin E groups showed a significant increase of total cholesterol of plasma, erythrocytes and liver and also an increase in plasma phospholipid and triglyceride levels was observed. But erythrocytes and liver phospholipid levels in high choesterol and high cholesterol plus vitamin E groups remained unchanged. There were no significant differences in plasma, erythrocytes and liver total cholesterol levels between high cholesterol and high cholesterol plus vitamin E groups. The plasma triglyceride level was significantly decreased in the high cholesterol plus vitamin E group in comparison to the high cholesterol group. On the other hand, lipid peroxide levels in the high cholesterol group significantly elevated in comparison with the control group. On the contrary, the high cholesterol plus vitamin E group showed a significant decrease in the lipid peroxide levels of plasma, erythrocytes and liver compared to that of high cholesterol group. The glutathione content was found to be significantly lower than the control group. Following vitamin E supplementation, glutathione content was significantly higher in plasma, erythrocytes and liver. The Na+-K+-ATPase and Ca+2-ATPase activities of erythrocytes and liver in high cholesterol group significantly decreased when compared with controls. On the other hand, high cholesterol plus vitamin E injection to the rats suppressed the reduction of Na+-K+-ATPase and Ca+2-ATPase activities in these tissue membranes. In conclusion, long-term administration of vitamin E may be useful in preserving of membrane asymmetry by suppressing the oxidative stress.