[Abstract] Objective The present study was performed to investigate the possible role of spinal cord chemokine (C-C motif) ligand 2 (CCL2) in morphine antinociceptive tolerance. Methods Morphine antinociceptive tolerance was induced by intrathecal administration of 15 mg of morphine daily for 7 days. The role of CCL2 in morphine antinociceptive tolerance is explored by hot-water tail-flick test. ELISA（enzyme-linked immunosorbent assay ）was used to test the change in spinal CCL2 immunoreactivity .Results On the 3rd ﹑5th and 7th day after chronic morphine , The %MPE （percent of maximal possible antinociceptive effect）were significantly decreaced in CCL2 neutralizine antibody plus morphine group as compared with IgG plus morphine group(P＜0.05，P＜0.01),The %MPE were significantly up-regulated in CCL2 neutralizine antibody plus morphine group as compared with IgG4 plus morphine group(P＜0.01); On the9th and 11th day after chronic morphine,The %MPE were significantly up-regulated in CCL2 neutralizine antibody8 plus morphine group as compared with IgG8 plus morphine group(P＜0.05，P＜0.01); On the 3rd ﹑5th and 7th day after chronic morphine:CCL2 expression in IgG plus morphine group were significantly up-regulated as compared with IgG plus saline group(P＜0.05，P＜0.01), While the CCL2 expression in CCL2 neutralizine antibody plus morphine group were significantly down-regulated as compared with IgG plus saline group(P＜0.05，P＜0.01).Conclusions spinal CCL2 is involved in the development and maintenance of tolerance to morphine-induced analgesia. Inhibition of CCL2 may provide a new therapy for morphine tolerance management.