Abstract: The aim of the present study was to investigate the effects and mechanisms of quercetin on plantar incision-induced matrix metalloproteinase(MMP)-9 and MMP-2 activity, microglia activation and the analgesic effect of quercetin on plantar incision surgery-treated mice. Postoperative pain model was mediated by plantar incision surgery and Von Frey Hairs was used to test the mechanical pain threshold. The activity of MMP-9 and MMP-2 in spinal cord was evaluated by gelatin zymography. The marker of microglia ionized calcium binding adapter molecule 1(IBA-1), phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK)was detected by Western blot. Results showed that quercetin(20, 40, 80 mg/kg, ip)significantly inhibited plantar incision-induced mechanical allodynia and suppressed the activity of MMP-9 and MMP-2 in the spinal cord. Moreover, quercetin also markedly inhibited plantar incision-induced up-regulation of IBA-1 and p-p38 in spinal cord. In conclusion, quercetin may alleviate postoperative pain by suppressing MMP-9 and MMP-2 activity in microglia.