[Abstract] Objective To investigate the antinociceptive effect of hyperbaric oxygen (HBO) on activation of microglia in rats with neuropathic pain produced by chronic constriction injury of the sciatic nerve (CCI). Method Twenty-four healthy male Sprague-Dawley rats were randomly divided into four groups(n=6): Sham group (group S), CCI group (group C),2.0ATA HBO post-conditioning group (group H2.0) and 2.5ATA HBO post-conditioning group (group H2.5).Group CCI, group H2.0 and group H2.5 were received the surgery of the chronic constriction injury. One day after surgery HBO of 2.0 ATA and 2.5 ATA was given respectively by hyperbaric oxygen cabin once a day for seven days in group H2.0 and group H2.5. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of rats in each group were measured respectively on day 1 pre-surgery (baseline) and every day during 7 days post-surgery. The rats were killed at the time when MWT and TWL had were measured at 7d after surgery. The lumbar segment L4-5 of the spinal cord was removed.Immunohistochemical technique was used to detect the activation of microglias in the spinal cord. Result Compared with group S, MWT and TWL were significantly decreased and the activation of microglias in the spinal cord was significantly enhanced after surgery in group C(P<0.05). Compared with group C, MWT and TWL were significantly increased and the activation of microglias in the spinal cord was significantly inhibited after surgery in group H2.0 and H2.5 (P<0.05). There was no significant difference in the activation of spinal microglias between group H2.0 and H2.5 Conclusion HBO post-conditioning produce the antinociceptive effect by inhibiting activation of spinal microglias in rats model of neuropathic pain.