To investigate the role of endogenous heme oxygenase (HO)/carbon monoxide (CO) system in the lung injury as assessed by lung histology, polymorphonuclear count, malondialdehyde content and wet-to-dry weight ratio following ischemia-reperfusion (I/R) of hind limbs, zinc protoporphyrin (ZnPP), an inhibitor of HO activity, was used, and the lung HO activity and blood carboxyhemoglobin (COHb) level were measured. The results showed that HO activity and COHb level were increased significantly and lung injury occurred after limb I/R. After administration of ZnPP, the lung injury was further aggravated while the HO activity and COHb level were significantly decreased. These findings suggest that upregulation of HO activity followed by subsequent CO production attenuates the lung injury induced by limb I/R in rats.