The current study was designed to evaluate the efficacy of both DMPS (2-3-Dimercapto-1-Propane Sulfonic acid) and DMSA (Meso-2,3-Dimercapto Succinic acid) in  treatment of long-term lead toxicity through assessment of some biochemical indices and levels of lead in liver, kidney and brain of exposed rats. One hundred twenty male albino rats were divided into four equal groups. The first group (I) was used as control, the 2^nd, 3^rd and 4^th (II, III, IV group respectiveIy) were exposed to 100 ppm lead acetate in drinking water for 12 weeks. Groups III and IV were treated with DMSA and DMPS respectively after 2, 4, 6, 8, 10, 12 weeks 24 hours prior to sampling. The investigated parameters were ALT, AST, γ–GT, LPO, NO and SOD. Lead levels in liver, kidney and brain were estimated. The results revealed that, both DMPS and DMSA induced many positive effects on lead exposed rats. These effects include, decrease the levels of LPO and NO especially in the first six weeks of the experiment, increase the level of SOD enzyme in both serum and brain tissues at the last six weeks of the experiment, decrease the lead levels in the tissues of the kidney and liver in group III allover the experimental period, while in group IV the decrease was only significant at the first weeks, and significant decrease in the brain lead levels in group III at the last six weeks of the experiment. These results indicated that Both DMSA and DMPS improve the biochemical, free radicals and antioxidant parameters in their groups in comparison with Lead treated group. DMSA have a better effect in reducing lead levels in liver and kidney during the whole period of the experiment and reduced lead level in brain tissue at the last sex weeks of the experiment.