The present study was carried to evaluate the protective effects of alpha-lipoic acid against lead (Pb) induced oxidative stress to erythrocytes in rats. Eighty male albino rats were divided into four groups containing 20 rats each. Group I: (control) administered distilled water. Group II :( Lead exposed group) received lead acetate (30 mg/kg body weight of 1/20th of LD50) orally and once per day over a period of 10 weeks. Group III :( Lead+Alpha-lipoic acid treated group) received lead acetate (30 mg/kg body weight) and treated daily with alpha-lipoic acid (54 mg/kg body weight/ i.p). Group IV:( alpha-lipoic acid treated normal group) (54 mg/kg body weight/ i.p).Serum used for determination of nitric oxide (NO), urea, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST) activities, tumor necrosis factor-alpha (TNF-α) , interleukin-6 (IL-6) , interleukin-1B (IL-1B) and Moreover, erythrocyte hemolysate were processed for the determination of L-Malondialdhyde (L-MDA), catalase (CAT), superoxide dismutase (SOD) ,Glutathione peroxidase (GPx ) and reduced Glutathione (GSH). The obtained results revealed that, a significant increase in serum urea, creatinine and ALT, AST and (TNF-α), interleukin-6 (IL-6), interleukin-1B (IL-1B) concentrations and hemolysate L-MDA level were observed in lead intoxicated rats. However, administration of alpha-lipoic acid in lead intoxicated rats exhibited a significant decreased in all mentioned parameters. On the other hand, a significant decreased in erythrocyte CAT, SOD and GPx activities, and GSH concentration were observed in lead intoxicated rats. Meanwhile, alpha-lipoic acid administrations in lead intoxicated rats resulted in significant increase in all mentioned parameters. It could be concluded that, the potential of alpha-lipoic acid as a powerful agents and may be useful as an antioxidants in combating free radical-induced oxidative stress and tissue injury that is a result of lead toxicity. Also, these compounds could be also applicable as a cytoprotective against oxidative stress of tissue damage mediated by heavy metals intoxication.