Diabetes mellitus is a major cause of impaired tissue repair. Patients with this disease not only have a propensity to develop wounds, but when they do, they tend to have difficulty healing those wounds. Simple wounds often become chronic and infectious wound complications are not uncommon. Unfortunately, the amputation rate for diabetics is much higher than for the nondiabetic population. Because healing problems are so common and devastating, several models of tissue repair have been developed in animals that are “made” diabetic or have a genetic predisposition for diabetes mellitus. The goal of this chapter is to review these models and to try to relate their similarities to human diabetes mellitus. It must be remembered, however, that diabetes mellitus is a very complex spectrum of diseases and that no animal model completely represents all human forms. It is important to choose a model that answers the question that the investigator is asking. By understanding how the various models relate to different aspects of human diabetes mellitus, the investigator can choose the correct model for the proposed studies.