BACKGROUND In 2010, the world prevalence of diabetes is 6.4%, affecting 285 million adults. Diabetic patients are at risk of developing neuropathy and delayed wound healing that can culminate in incurable diabetic foot ulcerations (DFUs) or even foot amputation. METHODS The contrast between cellular and molecular events of wound healing and diabetic wound healing processes is characterized. Neuropeptides released from the autonomous nervous system and skin cells reveal a major role in the immunity of wound healing. Therefore, the signaling pathways that induce pro/anti-inflammatory cytokines expression and its involvement in diabetic wound healing are discussed. The involvement of neuropeptides in the activation, growth, migration and maturation of skin cells, like keratinocytes, Langerhans cells, macrophages and mast cells, are described. RESULTS This review attempts to address the role of neuropeptides in skin inflammation, focusing on signal transduction, inflammatory mediators and pro/anti-inflammatory function, occurring in each cell type, as well as, its connection with diabetic wound healing. CONCLUSIONS Understanding the role of neuropeptides in the skin, their application on skin wounds could be a potential therapy for skin pathologies, like the problematic and prevalent DFUs.