During the perinatal period, the pharmacokinetics and pharmacodynamics of drugs may be altered. Data about the neurotoxicity of intrathecal local anesthetics in the peripartum period are lacking. So we hypothesized that the neurotoxicity of intrathecal lidocaine during perinatal period may be changed. Therefore, we designed the present study to determine whether the neurotoxicity of intrathecal lidocaine in postpartum rats would be different from that in nonpregnant, virgin rats. Postpartum and nonpregnant rats randomly received an intrathecal infusion of lidocaine 50mg/mL in saline, lidocaine 20mg/mL in saline, or saline for 1h at a rate of 1L/min. Four days after drug infusion, the rats were assessed for persistent impairment of sensory and motor function (MF) using the tail-flick (TF) test, paw pressure test, and MF score. Spinal cords and nerve roots were obtained for light and electron microscopic examinations, and the injury scores were compared between groups. The TF latencies and the mean nerve injury scores of the postpartum group were significantly higher than those of nonpregnant group. Lidocaine induced a dose-dependent impairment in TF latencies and nerve injury scores. There was no significant interaction between postpartum and the drug. Our results suggest that the neurotoxicity of intrathecal lidocaine is enhanced in rats during the early postpartum period compared with nonpregnant, virgin rats.