Although systemic lidocaine has been shown to suppress postoperative pain in a clinical setting, the mechanisms of action of lidocaine have not been elucidated. The present study was therefore designed to determine the relative contribution of central and peripheral sites to the action of lidocaine on incision-induced hyperexcitation of spinal dorsal horn (SDH) neurons in the rat. Receptive field (RF) areas, spontaneous activities, and responses of single wide-dynamic-range (WDR) neurons of the SDH to nonnoxious and noxious stimuli were recorded before and after longitudinal incisions of 1 cm through the skin, fascia, and muscle had been made in the center of their RFs of the hindquarters. Significant increases in spontaneous activities, RF sizes, and responses of WDR neurons to both nonnoxious and noxious stimuli were observed at 30 min after the incision (P < 0.001). Systemic administration of lidocaine (1 mg/kg bolus plus 0.5 mg/kg/h and 2 mg/kg bolus plus 1 mg/kg/h) and QX-314 (1 mg/kg bolus plus 0.5 mg/kg/h and 2 mg/kg bolus plus 1 mg/kg/h) significantly but temporarily suppressed and reversed the increases in spontaneous activity, responses to nonnoxious, and noxious stimuli and RF sizes (P < 0.01). Systemic administration of the same doses of lidocaine and QX-314 did not affect responses of WDR neurons to nonnoxious or noxious stimuli or their RF sizes in sham-operated animals in which an incision had not been made. The results suggest that systemic administration of lidocaine has suppressive effects on postoperative pain mainly through peripheral sites of action.