Oxidative stresses such as oxidant stimuli, inflammation, exposure to xenobiotics, and ionizing irradiation elicit various tissue injuries and provoke cellular responses, principally involving transcriptional activation of genes encoding proteins which participate in the defense reactions (Camhi et al., 1995). One of them is micro-somal heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, as well as the 32-kDa heat shock protein. In an oxidative tissue injury, HO-1 induction confers protection, while its abrogation accelerates cellular injuries (Otterbein and Choi, 2000). In this context, HO-1 plays a major protective role against oxidant stimuli. In this article, we summarized recent evidence from our laboratory as well as from others on the role of HO-1 in the reperfusion injury, and the oxidative tissue injury by volatile inhaled gases.