CGRP-expressing nociceptive sensory neurons promote tissue healing by modulating immune cells, particularly neutrophils and macrophages. Ablation of NaV1.8 nociceptors impairs skin wound healing and muscle regeneration after injury. During healing, nociceptor endings signal to immune cells via CGRP, which acts through RAMP1 to inhibit neutrophil recruitment, accelerate cell death, enhance efferocytosis, and polarize macrophages toward a pro-repair phenotype. CGRP's effects are mediated by thrombospondin-1 (TSP-1) release, which has autocrine and paracrine effects. In diabetic mice with peripheral neuropathy, engineered CGRP (eCGRP) accelerates wound healing and muscle regeneration. CGRP regulates myeloid cell function by inhibiting migration, promoting cell death, enhancing efferocytosis, and inducing macrophage polarization toward an anti-inflammatory and pro-repair state. TSP-1 mediates these effects by limiting neutrophil accumulation and accelerating cell death in the presence of inflammatory cytokines. Local delivery of eCGRP improves tissue healing in diabetic mice by reducing pro-inflammatory markers and increasing anti-inflammatory markers. These findings highlight the importance of neuro-immune interactions in tissue healing and suggest that harnessing this axis could lead to effective therapies for non-healing tissues, including those in diabetic patients.CGRP-expressing nociceptive sensory neurons promote tissue healing by modulating immune cells, particularly neutrophils and macrophages. Ablation of NaV1.8 nociceptors impairs skin wound healing and muscle regeneration after injury. During healing, nociceptor endings signal to immune cells via CGRP, which acts through RAMP1 to inhibit neutrophil recruitment, accelerate cell death, enhance efferocytosis, and polarize macrophages toward a pro-repair phenotype. CGRP's effects are mediated by thrombospondin-1 (TSP-1) release, which has autocrine and paracrine effects. In diabetic mice with peripheral neuropathy, engineered CGRP (eCGRP) accelerates wound healing and muscle regeneration. CGRP regulates myeloid cell function by inhibiting migration, promoting cell death, enhancing efferocytosis, and inducing macrophage polarization toward an anti-inflammatory and pro-repair state. TSP-1 mediates these effects by limiting neutrophil accumulation and accelerating cell death in the presence of inflammatory cytokines. Local delivery of eCGRP improves tissue healing in diabetic mice by reducing pro-inflammatory markers and increasing anti-inflammatory markers. These findings highlight the importance of neuro-immune interactions in tissue healing and suggest that harnessing this axis could lead to effective therapies for non-healing tissues, including those in diabetic patients.