Curcumin, the yellow pigment in turmeric, is present in the rhizomes of the plant Curcuma longa. Mercury (HgCl2) induces various toxic effects in different organs of the body. The present work was undertaken to evaluate the beneficial effect of curcumin following mercuric chloride induced oxidative stress in rat brain. The antioxidative indices assayed were superoxide dismutase, glutathione peroxidase, glutathione reductase, thiobarbituric acidreactive substances and total –SH groups. Metabolic parameters like total protein, cholesterol, succinate dehydrogenase, adenosine triphosphatase and mercury levels were also measured. Mercury exposure resulted in a significant increase in thiobarbituric acid-reactive substances and mercury levels. Contrarily a decrease in the activities of most of those enzymes, total –SH groups, protein and cholesterol levels were noted. Curcumin administration reduced TBARS and mercury levels, whereas it enhanced the other enzyme activities, total –SH groups, proteins and cholesterol levels comparable to controls. In summary, curcumin administration protects different parts of the brain against mercuric chloride induced neurotoxicity. Introduction Mercury is released into the environment through various natural geological processes, such as volatilization of rocks, dissolution, and volcanic eruption as well as due to some anthropogenic activities like combustion of fossil fuels, incineration of waste, mining and industrial discharge (Agrawal and Baheri, 2007). The cellular mechanisms by which mercury compounds exert their neurotoxic action were obtained from in vitro studies. Sorg et al. (1998) proposed that the mechanism of mercury toxicity could be via binding to thiol groups. Mercury compounds can inactivate a number of enzymes by blocking the functional sites binding to -SH groups, which are part of the catalytic or binding domains. Mercury treatment induced the dramatic increase in reactive oxygen species accumulating in rat brain cell cultures, leading to increased lipid peroxidation, protein degradation, and finally to cell death (Sorg et al., 1998). Rats and mice injected with inorganic mercury were detected with mercury granules in the different regions of the nervous system (Neustadt and Pieczenik, 2007). Mercury treatment exerted significant increase in ROS only in the cortical region and marked dose dependent increase (2500-5600-fold) in total Hg in the different brain regions (Goering et al., 2002). Morphological changes and Hg accumulation are different between cerebral hemisphere and cerebellar astrocytes after mercury treatment cultured from newborn rats (Adachi and Kunimoto, 2005). Pregnant female rats exposed to a very low dose of inorganic mercury from prenatal day 0 continued to postnatal day 20, the highest Hg content was present in the infant hippocampus and cerebellum, whereas its content in maternal brain regions like cerebrum, cerebellum, brain stem, hippocampus and thalamus (Feng et al., 2004). However, the role of herbal antioxidants on metal exerted neurotoxicity is attained less attention. Hence, this study was proposed to investigate the ameliorative effect of curcumin powder on regional brain toxicity induced by mercury in the rat. Rao et al. (2009) also studied effects of Hg in different regions of male rat brain affecting it in a dose dependent manner and role of melatonin on its toxicity. Materials and Methods Male Wistar strain Albino rats (Rattus norvegicus), weighing 200-250gms were procured from Cadila Pharma, under the Animal maintenance and Registration No.167/1999/CPCSEA from the ministry of Social Justice and empowerment, Govt. of India. The rats were fed on the standard commercial laboratory chow and distilled water ad libitum and were housed in the plastic cages with good ventilation. Light dark conditions as well as temperature was maintained (12h: 12h and 26±2oC respectively) throughout the seasons. Animals were assigned to 5 groups of 8 rats each. Group I served as control and animals were provided with distilled water. Group II animals received (low dose) HgCl2 (2mg/kg body weight) orally. Group III was administered with 4 mg/kg body weight (high dose) of mercuric chloride. Group IV received curcumin alone (80mg/kg body weight) and Group V received curcumin along with high dose of HgCl2. All the treatments were administered for 2 months and on the 61st day the animals were weighed and necropsy was performed. The brain was dissected carefully and weighed. Experiments were carried out on cerebral hemisphere and cerebellum. Antioxidant parameters The antioxidant enzyme activities like superoxide dismutase (SOD, EC:1.15.1.1), glutathione reductase (GR, EC:1.6.4.2), glutathione peroxidase (GPx, EC:1.11.1.9) were analysed by the spectrophotometric method of Kakkar et al. (1984), modified method of Pagila and Valentine (1967) and the method of Carlberg and Mannervik (1985) respectively. Thiobarbituric acid-reactive substances (TBARS) were determined by Ohkawa et al., (1979). Biochemical parameters The methods of total (-SH), succinate dehydrogenase (SDH, EC:1.3.99.1) and adenosine triphosphatase (ATPase, EC:3.6.1.3) was carried out by the methods of Sedlak and Lindsey (1968), Beatty et.al., (1966) and Quinn and White (1968) respectively. Total proteins and Cholesterol were determined by the methods of Lowry et al., (1951) and Zlatkis et. al., (1953) respectively. Mercury levels in the brain were estimated using mercury analyzer (MA 5840, Electronic Corporation of India Ltd., Hyderabad) using acid digestion method followed by cold vaporization of the sample. Data were statistically analyzed by Student’s t-test and ANOVA. Results Antioxidant system. In the present study antioxidant enzymes such as SOD, GPx, and GR were significantly (P