Objective To establish rat models of chronic skin ulcers by various methods and compare the differences and characteristics of the different models through various indexes. Methods Male SD rats were randomly divided into four groups and treated with various factors after creating a wound surface by removing back skin: skin defect, hydrocortisone (skin excision + hydrocortisone intervention), hydrocortisone plus bacterial interference (skin excision + hydrocortisone + bacterial intervention), and implantation of a foreign body (skin excision + embedded foreign body) groups. The body weight and wound healing of rats were measured each day and the wound state was observed. Materials were drawn from all groups at 14 days after the operation to assess histological changes, the immune organ index, blood leukocyte level, hydroxyproline (Hyp), total protein, and tumor necrosis factor-α (TNF-α) content in the skin ulcer. Results No significant difference in the body weight of rats in each group was found during the experimental period. The skin wounds of rats in the skin defect group healed faster, the symptom duration of chronic skin ulcers in the hydrocortisone group was shorter, and the color of granulation tissues in the implantation of the foreign body group was gray in the early stage, but the granulation grew faster in the later stage, while the hydrocortisone plus bacterial interference group had yellow pus in wounds and slow growth of granulation tissue. Pathomorphological observation showed severe inflammatory cell infiltration in hydrocortisone plus bacterial interference and implantation of foreign body groups. Moreover, compared with the skin defect group, the model groups showed increases in the spleen index, leukocyte level, and hydroxyproline content in wound tissue (P< 0.05 or P< 0.01), and in the skin lesion+ hormone +bacteria group, total protein content was decreased obviously (P< 0.05), while TNF-α content was increased significantly (P< 0.05). Conclusions After applying various intervention factors based on full- thickness skin resection, the healing speed of rat skin ulcers was slower than that of simple skin resection. Among them, the pathological characteristics of the skin lesion + hormone + bacteria model were more stable and long lasting. It can be used as the preferred model of chronic refractory skin ulcers, whereas the skin excision + hydrocortisone intervention and skin excision + foreign body embedded models may be more suitable to study short-term refractory wounds, and the embedded foreign body can be used to observe the growth of simple granulation in the early stage.