Aluminum (Al) is a trace element available in the Earth’s crust naturally and also is the most toxic metals studied because it caused many affections in animals and human. It has been suggested as a contributing factor in the pathogenesis of encephalopathy, osteomalacia and microcytic anemia. So it causes many economical losses. Selenium (Se) is an essential trace mineral of primary importance for human and animal health. Vitamin E compounds and Selenium haveantioxidative characteristics which needed for the suitable function of the immune system. Meso-2,3-dimercaptosuccinic acid (DMSA) is a provocative chelation which bound to plasma albumin and appears to be excreted in the urine. Therefore, the present study has been designed to explore the protective effects of vitamin E & selenium and/ or DMSA against aluminum chloride intoxication in rats by monitoring hematological picture, serum testosterone hormone, Aluminum residues, lipid per oxidation, Nitric oxid, some antioxidant enzymes as catalase (CAT), glutathione peroxides (GPx) in brain and testicular tissues beside the pathological examination. 50 adult male albino rats were divided into five groups. The first group (group I) served as a control. The second group exposed to Aluminumchloride (AlCl3) twice weekly at a dose of 2 mg/kg b.w, twice / week, orally by stomach tube for three months. The third group received DMSA at a dose of 27 mg/kg b.w, twice/ week, orally by stomach tube in addition to AlCl in the same dose for 3 months. The fourth group (group IV) received Vitamin E & Selenium (1ml/ liter) in drinking water in addition to AlCl3 at the same dose for 3 months. The fifth group (group V) received Vitamin E & Selenium in drinking water and DMSA by stomach tube in addition to AlCl3 at the same doses for 3 months. Blood samples were taken for complete blood picture (CBC) also serum was obtained for determination of testosterone hormone levels as well as brain and testes tissue for biochemical parameters, AL residues estimation, and pathological examination . The results of hematological picture revealed that animals in group II showed a significant increase in WBCs, monocytes, lymphocytes, granulocytes and platelets when compared with other groups, while RBCs count significantly decreased. There was a highly significant increase in lipid per oxidation (MDA) and Nitric oxid in group II while GPx and CAT levels were significantly decreased. Rats in group II have a significantly higher concentration of AL in brain and testes tissue than in other treated groups specially group III and V. The histopathological examination of brain in group II showed demyelination, neuronal degeneration up to necrosis compared to other groups as well as degeneration of spermatogenic cell in the somniferous tubules of testes with formation of spermatid giant cells inside the lumen with interstitial inflammation and degeneration of pseudo stratified columnar epithelium of prostate gland. The results of this investiga- tion demonstrated that aluminum chloride toxicity induces morph pathological lesions in brain, testes and prostate gland. It decreases GPx and CAT activates. Vitamin E and selenium with DMSA have the best ameliorating effect against Al toxicity after three months post-treatment.