This study was conducted to explore the capability of PAS (Para- aminosalicylic acid) and HEDTA [N-(2-hydroxyethyl) ethylenediamine triacetic acid] either alone or in combination in reducing some oxidative changes in different brain regions (cerebral cortex, cerebellum and medulla oblongata) in rats exposed to manganese. Seventy five male weanling rats (PND 21) were divided into two groups, group (A) served as (-ve) control group (C1) and group (B) received manganese chloride tetrahydrate (MnCl₂. 4 H₂O) via drinking water for 60 days in a concentration of 5 mg MnCl₂/ ml of H₂O. Twenty four hours after cessation of Mn exposure, group B was divided into 5 subgroups. Rats of group B1 were killed directly after cessation of Mn exposure and served as +ve control group. Rats of group B2 received saline solution 0.9% intraperitoneally (i/p) for 4 weeks served as withdrawal group. Rats of group B3 received 200 mg PAS / Kg b.w. S/C daily for 5 days/week for 4 weeks, group B4 rats were received 50 mg HEDTA / Kg b.w. i/p daily for 5 days/week for 4 weeks and group B5 received mixture of both PAS and HEDTA in the same manner and concentration as in group B3 and B4. Animal groups treated with each chelating agent separately, recovered the neurotoxicity and oxidative stress induced by Mn. 4H₂O and that indicated by significant improvement in superoxide dismutase (SOD), catalase, AChE and glutathione peroxidase activity as well as marked decrease in TBARS and nitric oxide production as compared to Mn treated group. Withdrawal group showed no improvement in most of the previous parameters which may be attributed to the irreversible damage of Mn to the brain tissues.