Abstract: Background and Objective: Artemisia absinthium L. has long been used as traditional herbal medicine for the treatment of gastric pain, cardiac stimulation to improve memory and to restore declining mental function. Aim of the present study was designed to investigate the effects of Artemisia absinthium L. on cerebral oxidative stress induced by mercury. Aqueous extract (AEAA) (500 mg L–1 b.wt. day–1) was administered orally to experimental rat and brain injury was induced by administration of HgCl2 (5 mg kg–1 b.wt., i.p.). Methodology: The activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), Glutathione Reductase (GR), catalase (CAT) and thioredoxin reductase (TrxR) were measured in different brain regions: Cerebral cortex (CX), cerebellum (CE), hippocumpus (HI) and striatum (ST). Lipid peroxidation (LPO) and Protein Oxidation (PO) levels were determined by evaluated the levels of malondialdehyde (MDA) and Protein Carbonyl (PC). Results: Lipid peroxidation was significantly higher in all brain regions vs. control after HgCl2 treatment. In CX and HI, it is observed a significant depletion of activities, respectively in glutathione peroxydase (11 and 81%), glutathione reductase (32 and 15%), superoxide dismutase (98 and 77%) and catalase (18 and 44%). Further, thioredoxine system was also significantly impaired by mercury as compared with control group. Conclusion: Obtained results demonstrated that treatment with AEAA reduce significantly (p<0.001) MDA level by 26.99, 31.81 and 80.70% in CE, CX and ST, respectively and increase catalase activity in CE. Furthermore, AEAA significantly (p<0.001) restored activities of defense antioxidant enzymes SOD and GPx, GR and TrxR towards normal levels in brain regions.