The toxicity of mercury in humans and animals are well established and this depends greatly on the mercuric compounds. In this study Thespesia populnea has been investigated for its possible protective role in mercury induced cellular damage using Swiss albino mice. The liver marker enzymes SGPT and SGOT exhibited higher activity and the antioxidant enzymes CAT, GPx and GST in mercuric chloride [HgCl2] treated animals were lower. Liver histopathology showed that Thespesia populnea bark extract inhibited these amendments, had reduced fat cyst formation and developed binucleated cells induced by HgCl2 intoxication. From these results we conclude that enhanced levels of antioxidant enzymes and reduced amount of serum amino transaminase are responsible for the major protecting mechanisms of T. populnea bark extract in mercury induced oxidative stress in liver.