This study focuses on investigating the possible protective effect of sodium selenite (Na2SeO3) and/or vitamin E against mercuric chloride (HgCl2)-induced hepatotoxicity in rat. Male rats were given HgCl2 ( I mg/kg body weight (bw)) and HgCl2 plus Na2SeO3 (0.25 mg/kg bw) and/or vitamin E (100 mg/kg bw) daily via gavage for 4 weeks. HgCl2-treated groups had significantly higher white blood cell and thrombocyte counts than the control group. Serum activities of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl-transferase, and lactate dehydrogenase significantly increased and serum levels of total protein, albumin, triglyceride, total cholesterol, and low-density lipoprotein cholesterol significantly decreased in the HgCl2-treated groups compared with control group. Malondialdehyde level significantly increased and superoxide dismutase, catalase, and glutathione peroxidase activities decreased in liver tissue of HgCl2-treated rats. Also, HgCl2 exposure resulted in histopathological changes. Supplementation of Na2SeO3 and/or vitamin E provided partial protection in hematological and biochemical parameters that were altered by HgCl2. As a result, Na2SeO3 and/or vitamin E significantly reduced HgCl2-induced hepatotoxicity, but not protected completely.