Acetylsalicylic acid (ASA), a well-recognized non-steroidal anti-inflammatory drug (NSAID), is well known for the treatment of fever, pain alleviation and inflammatory conditions, especially for the prevention of cardiovascular complications and disorders. However, ASA has been reported to cause hepato-and gastro-toxicities. We evaluated the protective ability of α-tocopheryl acetate (Vitamin E, Vit E) against ASA-induced glutathione depletion, reduction in acetylcholinesterase (AChE) activity, Na + ,K + -ATPase activity and erythrocyte osmotic fragility in the red blood cells isolated from male albino rats. ASA significantly inhibited reduced glutathione (GSH) which was dramatically protected by Vit E. However, no detrimental activities of ASA were observed on glutathione reductase (GR) or glutathione peroxidase (GPx). Significant reduction of AChE activity in red blood cells was observed following treatment with ASA and Vit E significantly protected this detrimental effect. A small, but no-significant, elevation in the Na + ,K + -ATPase activity was observed following treatment with ASA and slight non-significant reduction was observed following treatment with Vit E. Similar results were observed in erythrocyte osmotic fragility experiment demonstrating % hemolysis in these red blood cells. Thus, Vit E may serve an adjunct preventative agent during the therapeutic treatment of ASA.