The purpose of this study was to investigate heme oxygenase-1 (HO-1) mRNA expression and bilirubin concentration alteration in humans exposed to acute hypoxia. Fourteen healthy adult males were randomly assigned to a sea level group and a hypoxia group, and then exposed to normoxia (400 m, 20.0 %O₂) and hypoxia (3,000 m, 14.5 %O₂) respectively, in a hypoxic chamber for 3 hours. SpO₂ during hypoxia were significantly lower than those at sea level (P＜0.05). Indirect bilirubin levels after hypoxia were significantly higher than those at sea level (P＜0.05). However, HO-1 mRNA expression was unaltered by hypoxia. In conclusion, our data indicate that an acute exposure to hypoxia at resting state for 3 hours might lead to antioxidative cytoprotective response without any increase in HO-1 gene expression.