BACKGROUND: The therapeutic effect of morphine on neuropathic pain states was controversial, but there are some reports that systemic morphine reduced pain. Recently, many investigators have reported that locally administered morphine alleviated pain in local inflammatory pain model. Therefore, we designed this study to evaluate the peripheral effect of morphine and its antagonism by naloxone in rats experiencing neuropathic pain. METHODS: Neuropathic pain was produced by tightly ligating the left 5 th and 6 th lumbar spinal nerves of male Spraw-Dawley rats. To evaluate the systemic effect, morphine 200 microgram was injected into the unaffected right paw. Morphine 50, 100 and, 200 microgram were injected into the affected left paw. Naloxone 5, 10 and 20 microgram were injected into the affected left paw ten minutes before morphine 200 microgram was injected into the affected left paw. Before and after drug injection, mechanical allodynia was quantified by the foot withdrawal frequency to von Frey filaments of 5.50 g or 1.48 g, applied to the affected left paw. RESULTS: Morphine 200 g injected into the unaffected right paw did not affect the foot withdrawal frequency on the affected left paw. Morphine 100 and 200 microgram decreased the foot withdrawal frequency. In rats with morphine 200 microgram injected into the left paw, naloxone 5, 10, and 20 microgram increased foot withdrawal frequency. Conclusion: These data represented that morphine injected into the affected paw dose-relatedly reduced mechanical allodynia via peripheral effect and pretreatment of naloxone significantly antagonized the morphine effect.