Objective To observe the effect of intrathecal p38 MAPK inhibitor (SB203580) treatment on neuropathic pain and the expression of p38 MAPK and BDNF in dorsal horn of spinal cord in rats with chronic constriction injury (CCI), So as to investigate the possible mechanisms of neuropathic pain. Methods Totally 30 SD rats were evenly randomized into 3 groups (n=10): sham group receiving intrathecal injection of sodium chloride, control group receiving intrathecal injection of sodium chloride and CCI surgery, and SB203580 group receiving intrathecal injection of SB203580 and CCI surgery. SB203580 (0.1 ml/kg) was administered 0.5 h before and 1-14 d after CCI surgery. The mechanical thresholds were tested 24 h before and 4-14 d after CCI surgery. p38 MAPK expression and BDNF release in the dorsal horn were determined using immunohistochemistry method 14 d after CCI surgery. Results The mechanical thresholds in the control and SB203580 groups were significantly lower after CCI surgery compared with that before CCI surgery (P<0.05), but there was no significant change in the control group(P>0.05). Compared with the sham operation group, the mechanical thresholds were significantly lower in the other two groups after CCI surgery (P<0.05). The mechanical threshold of SB203580 group was significantly higher than that of the control group after CCI surgery(P<0.05). The p38 MAPK expression and BDNF release were significantly higher in the control and SB203580 groups compared with those in the sham operation group (P<0.05), and those in the SB203580 group were significantly lower than those in the control group (P<0.05). Conclusion Intrathecal injection of p38 MAPK inhibitor SB203580 can attenuate hyperalgesia in CCI rats through decreasing p38 MAPK expression and BDNF release.