Lead toxicity is a worldwide health problem due to continues exposure of the population to lead in the environment and industries. It affects many organs especially the liver and kidneys. The aim of this study is to investigate and compare the therapeutic potential of alpha lipoic acid (ALA) when its administrated alone and in combination with succimer or dimercaptosuccinic acid (DMSA) against lead induced oxidative stress, hepatotoxicity and nephrotoxicity. Seventy five healthy male albino rats were used divided into 5 equal groups. Group (1) the control group was administrated distilled water orally for 5 weeks. Group (II) rats were given lead acetate (0.2%) in drinking water for 5 weeks. Group (III, IV and V) rats were given lead acetate (0.2%) in drinking water for 5 weeks followed by DMSA in a dose of 20 mg/kg body weigh/day intraperitoneally (i.p.) alone, ALA in a dose of 25 mg/kg body weigh/day (i.p.) alone and both drugs in combination during the 6th week only respectively. Rats were sacrificed after six weeks. Blood lead level, serum lipid peroxides (TBARS), serum total antioxidant (TAO) status and serum nitric oxide (NO) levels were measured. Liver function tests (serum alkaline phosphatase, glutamic oxalacetic transaminase and glutamaic pyruvic transaminase) were measured. In addition, kidney function tests (serum urea, creatinine and uric acid) were done. Results showed an increase in the mean of blood lead level, increase serum TBARS levels, decrease serum TAO and NO levels and increase levels of liver and kidney function tests in lead treated group. Treatment with DMSA alone resulted in reduction of blood lead levels, improvement of serum NO level but not decrease serum TBARS level and moderate decrease in the elevated liver and kidney function test parameters. Rats treated with ALA alone showed no reduction in the elevated blood lead levels, but decreased serum TBARS and improved serum NO, TAO levels, liver and kidney function tests. Rats treated with DMSA and ALA concurrently showed decrease in blood lead levels, decrease serum TBARS, increase serum NO and TAO levels to near normal level and corrected liver and kidney function tests. In conclusion administration of ALA has beneficial effect as thiol-mediated antioxidant function when given to occupationally exposed workers to lead and during treatment of lead toxicity as it increases the DMSA efficacy.