As a result of the stimulation of proinflammatory mediators, circulating peripheral-blood mononuclear cells migrate into the wound area, and they differentiate into different phenotypes of macrophage to take different roles in healing process. Their phenotypes interchange under different microenvironments. The disturbance of cutaneous environment in diabetic patients has been shown to alter the quantity, morphology, and functions of the macrophages resulting in retardation of wound healing. Healing of intractable diabetic wound can be improved by the supplement of exogenous growth factors, which might improve healing process by regulating the phenotype of macrophage in intractable diabetic wound. This article reviews the relationship between intractable diabetic wound and macrophage to explore new methods of treating intractable diabetic wound.