Abstract:Diabetic foot ulcer (DFU), one of the most severe complications of diabetes mellitus, imposes a significant clinical and socioeconomic burden on patients and healthcare systems. The development of animal models that can effectively recapitulate the pathophysiological processes of human DFU serves as a critical foundation for investigating its complex mechanisms and advancing effective intervention strategies. This paper systematically reviews the research progress of experimental animal models of DFU from a comparative medicine perspective, with a focus on comparative analysis of the advantages and limitations of different models.DFU animal models are broadly categorized into two major groups: diabetes mellitus models (including type 1 diabetes models, such as streptozotocin [STZ]-induced models; and type 2 diabetes models, including spontaneously mutated strains like db/db mice, ob/ob mice, and ZDF rats, as well as induced models such as high-fat diet combined with STZ) and ulcerative wound models (encompassing ischemic, neuropathic, infectious, and clinically symptomatic models). This review emphasizes species-specific differences in wound healing and their implications for translating research findings to clinical practice: rodents primarily rely on contraction of the subcutaneous fascia for wound closure, whereas humans depend predominantly on re-epithelialization and granulation tissue formation. Parameters including gender and age exert substantial influences on model construction and phenotypic manifestations. Looking ahead, emerging technologies—including humanized models, 3D bioprinting, and multigene-engineered animal models—are expected to provide more precise experimental platforms for basic and translational DFU research.