Objective To investigate the role of C-C motif chemokine ligand 3 (CCL3) in streptozotocin (STZ)-induced diabetic neuropathic pain in rats. Methods Sprague-Dawley rats were randomly divided into a control group and an STZ group. The rats in the STZ group were injected intraperitoneally with STZ and those in the control group were injected with the same amount of normal saline. The STZ group was further divided into CCL3, IgG2A, A438079 [selective antagonist of purinoceptor P2X7 (P2X7R)] and PBS subgroups; and CCL3, IgG2A, A438079 and PBS were injected intrathecally into the corresponding subgroups once a day from the day before STZ injection for 7 consecutive days. The expression of Iba1 after STZ administration in the spinal dorsal horn (SDH) was detected by immunohistochemistry. The expressions of CCL3, chemokine receptor CCR5 and P2X7R mRNAs were evaluated by qRT-PCR. Mechanical withdrawal threshold was measured after STZ administration by von Frey filament test. Results In the STZ group there was a remarkable decrease in paw withdrawal threshold in response to mechanical stimulation (P < 0.05), and a significantly increased number of microglia in the SDH (P < 0.05). Meanwhile, STZ-treated rats showed a significant increase in the expressions of CCL3 and CCR5 mRNAs in the SDH (P < 0.05). Intrathecal administration of the CCL3-neutralizing antibody attenuated the development of STZ-induced mechanical allodynia (P < 0.05). A438079 had preventive effect on STZ-induced allodynia (P < 0.05). Conclusions Our findings suggest a contribution of CCL3 and P2X7R in the SDH to STZ-induced allodynia.