AIM: To study the effect of carbon monoxide (CO) on hypoxia inducible factor-1? (HIF-1?) expression and on hypoxic tolerance duration in hypoxia preconditioned mice. METHODS: Mice were injected with normal saline (NS) or hemin intraperitoneally. Western blot was used to detect HIF-1? in hippocampus. The tolerant duration of each hypoxic run was recorded. RESULTS: After 1 and 2 runs of hypoxia exposure, there were no significant differences in HIF-1? expression and hypoxic tolerance duration between N and hemin injection groups. After 3 and 4 runs of hypoxia exposure, the content of HIF-1? was lower and hypoxic tolerance duration was shorter ( P