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The hepatoprotective effect and antioxidant activity of ethanol extract of Amaranthus hypochondriacus seed (ESAH) were evaluated in sodium arsenite (SA) treated rats. Animals were divided into eight groups. The first group was used as control, group II was administered SA (2.5 mg/kg body weight). Groups III, IV and V were administered different doses of ESAH (100, 200 or 300 mg/kg b.w., respectively); groups VI, VII and VIII were administered ESAH at 100, 200, 300 mg/kg b.w. plus 2.5 mg SA/kg; respectively. Rats were orally administered different doses of ESAH daily for fourteen days. The SA was administered on the 7th and 14th day. Results showed that sodium arsenite-induced elevation of alanine aminotransferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) levels were substantially reduced by pre-treatment with 200 and 300 mg/kg b.w. of ESAH. Histopathological observations also showed hepatic protective activity of ESAH. Sodium arsenite increased the concentrations of malondialdehyde (MDA), hydrogen peroxide and reduced the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and increased frequency of micronucleated polychromatic erythrocytes. Pre-treatment with 200 and 300 mg/kg of ESAH reduced the levels of MDA and H2O2; increased the activities of antioxidant enzymes (SOD, CAT, GPx) and reduced frequency of induction of micronucleated polychromatic erythrocytes (mPCEs) in bone marrow cells of the rats. Treatment with SA decreased body weight and increased relative liver weight compared to control and ESAH. Thus ESAH mitigates arsenic-induced hepatotoxicity and oxidative damage in rats. Key words: Amaranthus hypochondriacus, antioxidant enzymes, hepatoprotective effect, sodium arsenite.