Objective To explore the effect of hyperbaric oxygen therapy (HBOT) on the expression of AQP-4 and the brain edema to discuss the possible mechanisms of HBOT in the treatment of trauma brain injury. Methods Male Sprague-Dawley rats were randomized into sham-operated group, trauma control group and HBOT group (n=32); and then, the later 2 groups were subdivided into 4 groups according to the injury times (12 h, 1, 3 and 5 d), respectively (n=8). Feeney's brain injury models were induced; the water content of the brain tissue was measured by dry-wet method; the expression of AQP-4 was detected by immunohistochemical staining. Results The water content of the brain tissue in the HBOT group was significantly decreased as compared with that in the trauma control group, but significantly increased as compared with that in the sham-operated group (P<0.05). The protein expression level of AQP-4 was noted in all the brain tissues with the lowest level appearing in the sham-operated group. Increased protein expression of foot process AQP-4 was found in astrocyte cells of the contusion marginal region in the trauma control group 12 h after the operation, reaching its summit at 1d and starting to decrease at 3 d. The expression of AQP-4 in the HBOT group was decreased significantly as compared with that in the trauma control group at each time points (P<0.05).Conclusion HBOT may reduce the chance of brain edema and protect the brain tissue by decreasing the expression of AQP-4.