ABSTRACT Membrane lipids specially fatty acids appear to be one of the critical target associated with lead intoxication. The aim of our research was to elucidate the changes in erythrocyte membrane fatty acids composition, cholesterol and phospholipids (that may affect different aspect of cell structure and function) under the effect of chronic lead toxicity and their modulation with vitamin E. For this purpose forty two male new-Zealand rabbits of 2-3 months old, average body weight 2-3 kg were randomly divided into three equal groups, each of 14 animals, the first group (GI) kept as control. The second group ( G II) received orally lead acetate (l/20 of L.D.50) daily for 90 days, The third group (G III) administrated orally (lead acetate + vitamin E) daily for 90 days. Heparinized blood samples were obtained from all groups, plasma was separated and used for determination of lipid peroxidation (L. malondialdehyde). Red blood cells were processed for determination of cholesterol, phospholipids and fatty acid composition in erythrocytes membrane. Our data revealed significant increase in plasma MDA level (P < 0.001) and erythrocyte membrane cholesterol (P < 0.05) in lead intoxicated group, which decreased after vitamine E treatment. Whereas a significant decrease in membrane phospholipids and alteration in fatty acid pattern which also modulated by vitamin E supplementation.