Skin is a complex tissue, which comprises multiple layers. An injury to this stratified structure is considered to be the beginning of a sequence of events designed to restore skin integrity. Depending on the diameter and severity of a wound, deleterious physiological and metabolic changes can occur, leading to impaired wound healing and increased morbidity and mortality. While wound dressings provide some form of protection and remedy, the main challenge is to restore local metabolic pathways to normality, especially in the comprised patient suffering from chronic illness, such as diabetes. The implications of this disease in particular have prompted investigations into topical insulin as a potential and promising therapeutic intervention. This mini-review describes the possible mechanisms of insulin that are responsible for stimulating the cellular and molecular pathways, thereby enhancing the wound healing process. Examples of systemic and topical insulin applications are mentioned, together with an evaluation of the critical role played by insulin in tissue regeneration.