Heme oxygenase-1, a stress-responsive enzyme that catabolizes hemes into carbon monoxide, biliverdin, and iron, has been shown to play a pivotal role in many physiological and pathological situations. Here we investigated changes in HO-1 enzyme activity and protein expression, and its end product carbon monoxide concentrations in the liver of rats after CCl 4 treatment. We found that CCl 4 administration not only induced severe liver damage in rats, as demonstrated by dramatic elevation of ALT, AST levels and severe histopathological changes, but also resulted in a prominent up-regulation of HO-1 enzyme activity. Western blot and immunohistochemical analysis confirmed that expression of HO-1 protein was also increased significantly in a time-dependent manner following CCl 4 treatment, and localized mainly in liver cells around the central vein. In addition, CO concentrations in the liver of CCl 4 -treated rats were elevated remarkably in the same time-dependent way as HO-1 induction in contrast to the control rats. These data indicated that HO-1/CO pathway was greatly up regulated in the liver of rats after CCl 4 treatment, which might play an important protective role in the pathophysiological mechanism underlying CCl 4 -induced hepatotoxicity. It therefore suggested that more relevant studies should be carried out in the future to clarify the detailed mechanisms.