The protective effects of alpha-lipoic acid against lead (Pb) induced oxidative stress to kidney tissues in rats were evaluated. 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$. Also, kidney tissues were taken and processed for L-MDA, CAT, SOD,GPx, DNA fragmentation, caspase-3, NF-kB P65, 8-OhdG and Cox-2. Additionally, liver and kidney specimens were excised for histopathological examination and lead residues determination. The obtained results showed significant increase in serum TNF-", IL-6 and IL-1$, 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. The results indicate that, alphalipoic 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.