Nerve injury-induced axonal degeneration and subsequent axonal debris clearance were reduced in Tlr3−/− mice compared with wild-type mice. Nerve injury-induced macrophage infiltration into injury sites was also attenuated in Tlr3−/− mice, accompanied by reduced expression of the macrophage-recruiting chemokines, CCL2/MCP-1, CCL4/MIP-1β, and CCL5/RANTES. These data show that TLR3 signaling contributes to Wallerian degeneration after peripheral nerve injury by impacting Schwann cell activation and macrophage recruitment to injured nerves. This evidence concerns the gene CCL4 and peripheral nerve injury.