Objective To observe the effect of koumine on spared nerve injury(SNI)induced neuropathic pain(NP)and its possible mechanism with autophagy and astrocyte activation. Methods SNI rats and sham SNI rats were randomly assigned into five groups: the sham operation group, the SNI group, the koumine treatment groups(0.6 and 3 mg/kg), and the gabapentin control group(800 mg/kg). On postoperative day 3, the drugs or vehicle was administered intragastrically twice a day for 7 consecutive days. The mechanical pain threshold was measured on the day before surgery, on postoperative day 3(pre-dosing), and on 1 h after drug administration(post-dosing). At the end of the behavioural experiment, the spinal cord was obtained after perfusion fixation. The level of glial fibrillary acidic protein(GFAP), Beclin 1, LC3-Ⅱ, LC3-Ⅰ and p62 were measured by Western-blot. Results Koumine(3 mg/kg)and gabapentin had significant improved mechanical threshold of SNI rats. Koumine significantly reduced the GFAP level in the spinal cord of SNI rats. Koumine significantly enhanced the expression of LC3 and p62, but had no significant effect on Beclin 1. Conclusion These results suggest that the analgesic effect of koumine on SNI-induced NP may involve the inhibition of astrocyte activation and promotion autophagy in the spinal cord.