In this study, we investigate the efffects of curcumin trathecal injection on pain threshold and the expressions of TLR4, TNF-α, IL-1β and IL-10 in the spinal cord of rats with chronic constrictive injury (CCI). 120 males Sprague-Dawley (SD) rats fitted with intrathecal catheters were randomly divided into four groups: sham group (Sham), CCI group (CCI), solvent control group (SC), and curcumin treated group (Cur, 100 μg/d). Neuropathic pain was produced by CCI of right sciatic nerve as described previously. On the 1st, 3rd, 7th, 10th，and 14th day after surgery, 100 μg curcumin dissolved in DMSO 10 μl was administered intrathecally once daily, and then pain threshold was measured. The expressions of TLR4, HMGB1 mRNA, and protein in lumbar spinal cord 4～6(L4～L6) were assessed by RT-PCR and Western blotting, respectively. The levels of TNF-α, IL-1β and IL-10 in the spinal cord were detected by ELISA. We found that the paw withdrawl threshold (PWT) and paw withdrawl latency (PWL) were significantly decreased after CCI (P<0.05), and the expressions of TLR4, HMGB1 mRNA and protein were significantly increased (P<0.05); the levels of TNF-α and IL-1β in the spinal cord were also significantly increased after CCI compared with those in the sham goup (P<0.05). Curcumin markedly attenuated CCI- induced mechanical allodynia and thermal hyperalgesia through inhibiting the activation of TLR4 pathway and production of inflammatory cytokines. These results demonstrated that curcumin alleviated neuropathic pain may be by decreasing the expression inflammatory cytokines produced by TLR4 pathway.