Abstract: Objective To investigate the effect of systemic administration of gabapentin on the expression of TLR4 in dorsal root ganglion neurons in a rat model of diabetic neuropathic pain (DNP). Methods One hundred and eight male SD rats weighing 200-220g were randomly divided into 4 groups (n=27 each): control group (group Control), DNP group, saline group (SC+DNP group) and gabapentin +DNP group (GBP+DNP group). Diabetes was induced with streptozocin (70mg/kg) subcutaneously. Paw withdrawal mechanical threshold (PWMT) and Paw withdrawal thermal latency (PWTL) were measured at 1d before and 3d，7d，10d，14d，21d，28d after streptozocin injection and 21d，28d after administration of gabapentin (50 mg/kg/d，once) intraperitoneally. Saline and gabapentin (50 mg/kg/d) were given intraperitoneally once a day for 7 systemic and consecutive days starting from 15d after streptozocin injection in saline and gabapentin groups respectively. The expression of TLR4 was determined at 21d after streptozocin injection by immune-histochemistry and Western blot. Results Compared with group C, PWMT was significantly decreased, PWTL was significantly shorten, TLR4 in expression was significantly increased in DNP, SC+DNP group and GBP +DNP group (P＜0.05). Compared with SC+DNP group, PWMT was significantly increased PWTL was significantly prolonged, TLR4 expression was significantly decreased in GBP +DNP group (P＜0.05). There was no significant difference in the parameters mentioned above between DNP and SC+DNP group (P＞0.05). Conclusion Systemic administration of gabapentin attenuates diabetic neuropathic pain by inhibiting the expression of TLR4 in DRG neurons.