In this study, Li et al. investigated the mechanisms underlying the regeneration of peripheral nerves, which is guided by regeneration tracks formed through an interplay of many cell types. They demonstrate that macrophages are mobilized ahead of Schwann cells in the nerve bridge after transection injury to participate in building regeneration tracks. This requires the function of guidance receptor Plexin-B2, which is robustly up-regulated in infiltrating macrophages in injured nerve.