BACKGROUND: There have been some investigations regarding expression of c-fos, as a marker of altered neuronal expression in the spinal cord of neuropathic rats. However, the expression of c-fos in the brain of a neuropathic pain model has not yet been investigated. The purpose of this study was to evaluate the time course of c-fos expression in the brain of neuropathic pain rats. METHODS: The experimental rats were divided into two group; neuropathic pain (n = 16) and control (n = 16) groups. The left L5 L6 spinal nerves of the neuropathic pain group were ligated but those of the control group not ligated (sham operation). Two hours, 1st day, 3rd day and 7th day after the operation, we examined the expression of Fos in the cerebral cortex, the amygdala, the thalamus and the hypothalamus of the coronary sectioned brains of the rats. RESULTS: C-fos expressions in the cerebral cortex and the amygdala of the neuropathic pain group were greater at 2 hours, the 3rd and the 7th day than the control group, but those of the thalamus and hypothalamus of the neuropathic pain group were greater on the 3rd and 7th day than the control group (P< 0.05). In the neuropathic pain group, c-fos expressions of four brain regions were greater on the 3rd and 7th day than those at 2 hours and day 1, but there was no difference between the 3rd and 7th day's (P< 0.05). CONCLUSIONS: There were significant expressions of Fos protein in the brain of the neuropathic pain group at 2 hours, the 3rd day and 7th day of the operation, but the meaning of each expression was different. The expression of Fos at postoperative 2 hours resulted from acute pain but that at the 3rd and 7th day of the operation resulted from neuropathic pain.