The protective effects of alpha-lipoic acid against lead (Pb) induced oxidative stress to kidney tissues in rats were evaluated. Materials and Methods: Eighty male albino rats were divided into 4 equal groups. Group 1: (control) administered distilled water. Group 2 received lead acetate orally (30 mg kgG1 b.wt., of 1/20th of LD50). Group 3 received lead (30 mg kgG1 b.wt.) plus alpha-lipoic acid (54 mg kgG1 b.wt./day/i.p). Group 4: received alpha-lipoic acid (54 mg kgG1 b.wt.). Blood samples were collected for determination of serum TNF-", IL-6, IL-1$. Also, kidney tissues were taken and processed for L-MDA, CAT, SOD,GPx, DNA fragmentation, caspase-3, NF-kB P65, 8-OhdG and Cox-2. Additionally, liver and kidney specimens were excised for histopathological examination and lead residues determination. Results: The obtained results showed significant increase in serum TNF-", IL-6 and IL-1$, kidney tissues L-MDA, DNA fragmentation, caspase-3, NF-kB P65, 8-OhdG and Cox-2 in addition to liver and kidney lead residue in lead intoxicated rats. However, administration of alpha-lipoic acid exhibited a significant decreased in all mentioned parameters. Kidney tissues antioxidant enzymes were markedly decreased in lead intoxicated rats and the activities were attenuated after treatment with alpha-lipoic acid. Various pathological alterations were observed in liver and kidney of lead administered group. Interestingly, the histopathological results supported that alpha-lipoic acid markedly reduced the deleterious effect induced by Pb and preserved the normal histological architecture of the liver and kidney tissues. Conclusion: The results indicate that, alpha-lipoic acid could be applicable as a cytoprotective against oxidative stress of tissue damage mediated by heavy metals intoxication as confirmed by biochemical and histopathological results.