objective To observe the effect of intrathecal minocycline (a selective inhibitor of microglia) on mechanical withdrawal threshold (MWT) in a rat model of persistent postoperative pain evoked by skin/muscle incision and retraction (SMIR). Methods 32 male Sprague-Dawley rats were randomly divided into four groups(n=8): normal control group, sham operation group, SMIR model group and SMIR model plus intrathecal minocycline group(minocycline group). A PE-10 catheter was inserted into the subarachnoid space (intrathecal) according to the method described by Yaksh et al. A rat model of persistent postoperative pain evoked by SMIR was made according to the method described by Flatters. Pain behavior was assessed by mechanical withdrawal threshold (MWT) to von Frey filament stimulation intensity. Results Compared with both preoperative baseline and normal control group, the MWT in sham operation group did not change significantly; Compared with both preoperative baseline and sham operation group, the MWT in SMIR model group decreased significantly at postoperative days 3, 7, 12 and 22( P<0.05); Compared with SMIR model group, the MWT in minocycline group increased significantly at postoperative days 3, 7, 12 and 22( P<0.05). Conclusion Intrathecal minocycline markedly attenuates pain symptoms in a rat model of persistent postoperative pain evoked by SMIR, it suggests that activated spinal microglia plays an important role in the development and maintenance of persistent postoperative pain.