Objective To observe the effect of intrathecal CCL2 neutralizing antibody on pain behavior and the level of P-ERK1/2 expression in spinal cord in a rat model of bone cancer pain, then explore its possible mechanisms. Methods Thirty-two female SD rats weighting 180～220g were randomly divided into 4 groups(n=8): group Ⅰ, sham+ IgG group; group Ⅱ, sham + Anti-CCL2 intrathecal; group Ⅲ, model +IgG; group Ⅳ, model + Anti- CCL2. Rats in group Ⅰ and group Ⅱ were injected with 10μl Hank’s solution into the left proximal tibial medullary cavity; Rats in group Ⅲ and group Ⅳ were injected with 10μl Walker 256 breast cancer cells (1×107/ml) into the left proximal tibial medullary cavity. Von-Frey thresholds were measured before and at 1st, 3rd, 6th, 7th, 8th, and 9th day after surgery. The altered expression of p-ERK in spinal dorsal horn was detected by Western blot Results Compared with rats in group Ⅰ, Von-Frey thresholds significantly decreased in rats of group Ⅲ at the 6th day post-inoculation; Compared with rats in group Ⅲ, Von-Frey thresholds significantly decreased in rats of group Ⅳ at the 6th day post-inoculation. Compared with rats in group Ⅰ, the expression of P-ERK in spinal dorsal horn from group Ⅲ apparently increased (P<0.01). Spinal P-ERK1/2 protein levels of rats in group Ⅳ were lower than that of group Ⅲ. For GroupⅡ, There was no significant difference in the expression of spinal dorsal horn P-ERK between group Ⅰ and GroupⅡ. Conclusion Intrathecal CCL2 neutralizing antibody injection can partially release mechanical allodynia induced by bone cancer pain, which may be related to blockade of P-ERK1/2 in the spinal dorsal horn. These results indicate that spinal CCL2 may be involved in the development of rats bone cancer pain via activation of ERK in the spinal dorsal horn.