Gap-junctional connexin43 (Cx43) has roles in multiple aspects of skin wound healing – including scarring. The aim here was to study the effects of a cell-permeant peptide from the Cx43 carboxyl-terminus (CT) on scarring and regeneration following cutaneous injury. The effects of Cx43 CT peptide were studied in mouse and pig models of cutaneous injury. The parameters assessed included neutrophil density, wound closure, granulation, regeneration and skin tensile properties. Cx43 CT-peptide prompted decreases in area of scar progenitor tissue and promoted restoration of dermal histoarchitecture and mechanical strength following wounding of skin. These changes in healing were preceded by peptide-induced reduction in inflammatory neutrophil infiltration and alterations in the organization of epidermal Cx43, including increased connexon aggregation. Cx43 CT peptide promotes regenerative healing of cutaneous wounds and may have applications in tissues other than skin, including heart, cornea and spinal cord.