Recruitment of hematogenous myelomonocytic cells into injured peripheral nerve is essential for axonal regeneration. The monocyte chemoattractant protein-1 (JE) and melanoma growth stimulatory activity/gro (KC) “immediate early” gene products may be important in this process as these proteins are potent chemoattractants for macrophages and neutrophils, respectively. To test this hypothesis, we examined JE and KC activation in rat sciatic nerve 0-30 days after surgical transection. RT-PCR and in situ hybridization analyses of JE and KC expression demonstrates these mRNAs are present in injured nerve, first being expressed by a cellular subpopulation within the zone of trauma by 1.5 hours after injury. By 16 hours posttransection a subpopulation of JE-positive endoneurial cells is found in the proximal stump and throughout the distal nerve segment, with maximal mRNA accumulation occurring 1 day after injury and expression persisting to 18 days postaxotomy, a period preceding and coincident with macrophage infiltration. In contrast, by 3 days postaxotomy KC expression is markedly diminished, consistent with the limited neutrophilic response to nerve injury. JE expression was also examined in C57BL/ WldS mice, which have delayed Wallerian degeneration associated with a failure of macrophage recruitment, and their parental C57BL/6J strain. Although JE mRNA is inducible in sciatic nerve from C57BL/6J mice, these transcripts are undetectable in injured nerve from C57BL/WldS mice. Our findings suggest that activation of the JE locus is at least partially responsible for macrophage invasion of injured peripheral nerve. Furthermore, defective postaxotomy macrophage recruitment in C57B17 Wld1 mice may involve a failure of JE induction.