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 ulcer 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 such as humanized models, 3D bioprinting technology, and multi-gene edited or modified animal models will provide more precise experimental platforms for basic and translational research on DFU.