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<strong>Objective</strong> To observe the effect of early use of 0.25 MPa hyperbaric oxygen (HBO) on pain behavior in model rat of neuropathic pain (NP) and explore the mechanism. <strong>Methods</strong> Fifty-four male Sprague⁃Dawley (SD) rats were randomly divided into 3 groups (18 rats per group) including sham operation, sciatic nerve ligation with chronic constriction injury (CCI) and HBO early⁃treatment groups. The rat model of neuropathic pain was established, and CCI + HBO group received 0.25 MPa HBO treatment for 60 min per day at early stage, continuing for 5 d. The changes in general state of health, the number of paw withdrawal responses, paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were assessed at different time points after operation. <strong>Results</strong> Compared with sham-operated group, the body weight of rats in CCI group decreased significantly (t = 4.772, P = 0.000) on the 14th day; the body weight of rats in CCI + HBO group was significantly higher than that in CCI group (t = 2.411, P = 0.029). Compared with sham-operated group, reduced PWL immediately after operation (t = 28.345, P = 0.000), and more paw withdrawal responses (t = 12.541, P = 0.000) and decreased PWT (t = 4.032, P = 0.001) from the 3rd day after operation were observed in CCI group. Compared with CCI group, the number of paw withdrawal responses decreased (t = 8.077, P = 0.000), and PWT and PWL increased (t = 2.114, P = 0.049; t = 7.715, P = 0.000) in CCI + HBO group. <strong>Conclusion</strong> 0.25 MPa HBO treatment at early stage can ameliorate the mechanical and thermal hyperalgesia. HBO may provide a new convenient and effective way for the treatment of neuropathic pain in clinic.