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Resident and inflammatory macrophages are essential effectors of the innate immune system.These cells provide innate immune defenses and regulate tissue and organ homeostasis.In addition to their roles in diseases such as cancer,obesity and osteoarthritis,they play vital roles in tissue repair and disease rehabil itation.Macrophages and other inflammatory cells are recruited to tissue injury sites where they promote changes in the microenvironment.Among the inflammatory cell types,only macrophages have both pro-inflammatory (M1) and anti-inflammatory (M2) actions,and M2 macrophages have four subtypes.The co-action of M1 and M2 subtypes can create a favorable microenvironment,releasing cytokines for damaged tissue repair.In this review,we discuss the activation of macrophages and their roles in severe peripheral nerve injury.We also describe the therapeutic potential of macrophages in nerve tissue engineering treatment and highlight approaches for enhancing M2 cell-mediated nerve repair and regeneration.