Exposure to mercuric chloride (HgCl2; 5 mg kg−1 body weight; i.p.) induced oxidative stress in mice and substantially increased lipid peroxidation (LPO) and oxidized glutathione (GSSG) levels, decreased the level of reduced glutathione (GSH) and various antioxidant enzymes in liver and also increased the activities of liver marker enzymes in serum. Therapy with propolis extract, a resinous wax-like beehive product (200 mg kg−1 orally, after mercury administration), for 3 days inhibited LPO and the formation of GSSG and increased the level of GSH in the liver. Release of serum transaminases, alkaline phosphatase, lactate dehydrogenase and γ-glutamyl transpeptidase were significantly restored after propolis treatment. The activities of antioxidant enzymes, that is, superoxide dismutase, catalase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase, were also concomitantly restored towards normal levels after propolis administration. These observations clearly demonstrate that propolis treatment augments antioxidant defense against mercury-induced toxicity and provide evidence that propolis has therapeutic potential as a hepatoprotective agent.