In this study, the suppressive effects of BmK IT2, a kind of Na+ channel-specific modulator from the venom of the scorpion Buthus martensi Karsch, on biphasic nociceptive behavior in rats and c-Fos expression in rat spinal cord induced by formalin were investigated. Fifty microliters of 2.5% formalin were subcutaneously injected into the rat hind paw; 0.1 and 1 μg doses of BmK IT2 were subcutaneously administered into the rat ipsilateral hind paw 1 min before or 10 min after formalin injection individually, and the number of flinches per 5 min was counted. The detection of c-Fos expression induced by formalin in either the absence or the presence of BmK IT2 was carried out with the ABC method. Biphasic nociceptive behavior in rats was significantly suppressed by pretreatment with BmK IT2. No. of flinches/5 min in the second phase was also decreased by posttreatment with BmK IT2. In addition, c-Fos expression induced by formalin was significantly inhibited in all laminae of L4–5 spinal cord by pre- or posttreatment with BmK IT2. The suppression of BmK IT2 in the first- and second-phase behaviors may be attributed to the anesthesia of the toxin toward nociceptors and primary afferents and its selective modulation of tetrodotoxin-resistant Na+ currents of dorsal root ganglion neurons, respectively. In addition, the nonparallel suppression of BmK IT2 on flinch behavior and c-Fos expression induced by formalin may be ascribed to the different activity patterns of afferent fibers and central neurons. © 2003 Wiley-Liss, Inc.