AIM: To investigate the effect of hyperbaric oxygen (HBO) on gelatinase,nitric oxide synthase and the permeability of brain blood barrier(BBB) in ischemia-reperfusion(I/R) mice. METHODS: Using cerebral I/R models, during the reperfusion period, 0.25 MPa (ATA) HBO were applied 5 times. matrix metalloproteinase(MMP)-2,9, nitric oxide synthase(NOS) and evans blue (EB) in brain were measured. RESULTS: ①HBO had significanty effect on MMP-9, but had little effect on MMP-2. ② HBO decreased the activity of NOS.③ The maxium amount of EB in IR group was at 4 hours after reperfusion and gradually decreased at 11 h, 23 h,48 h, 72 h. CONCLUSION: HBO may decrease the activities of MMP-9,NOS and the permeability of BBB in cerebral ischemia-reperfusion mice.