Objective To explore Methods of streptozotocin-induced diabetic pulmonary fibrosis mouse model establishment and provide a stable animal model of diabetic pulmonary fibrosis for clinical research. Methods Sixty male C57BL/6 mice were randomly divided into three groups: normal control (NG, n= 20), diabetic pulmonary fibrosis 1 (DPF1, n= 20), and diabetic pulmonary fibrosis 2 (DPF2, n= 20) groups. The fasting blood glucose levels and body weight of the mice were measured after overnight fasting; then the DPF1 group was intraperitoneally injected with a large dose of streptozotocin (150 mg/ kg), and the DPF2 group was intraperitoneally injected with a small dose of streptozotocin (50 mg/ kg) every day for five consecutive days. The NG group was intraperitoneally injected with the same amount of sterile citrate buffer. After injection, the general condition of the mice was observed every day, and the body weight and random blood glucose of the mice were measured every week. The mice were fed normally for 16 weeks, and five mice were randomly selected from each group every 4 weeks to be sacrificed for pathology and molecular biology assays to assess the degree of pulmonary fibrosis. Results After streptozotocin induction, both the DPF1 and DPF2 groups had typical symptoms of diabetes including polydipsia, polyuria, polyphagia and weight loss. The body weight of the DPF1 and DPF2 groups increased slower than that of the NG group, and gradually decreased from the 8th week (P< 0. 05). The random blood glucose of the DPF1 and DPF2 groups was greater than 16. 7 mmol/ L after the 1st week and the 2nd week, respectively, and tended to be stable after the 9th week (P< 0. 05). The pathological results showed that, compared with the NG group, the DPF1 and DPF2 groups had no obvious fibrotic lesions at 4 weeks. However, a small number of fibrotic lesions were observed around the vessels at 8 weeks. Obvious fibrotic lesions were observed at 12 weeks, mainly accumulated around the blood vessels; and more obvious fibrotic lesions were observed at 16 weeks that involved the surrounding lung tissue. The molecular biological results were similar to the pathological results . Compared with the NG group, the DPF1 and DPF2 groups’ expression levels of mouse fibrosis marker collagen 3 did not change significantly at 4 and 8 weeks, but increased at 12 weeks (P< 0. 05) and significantly increased at 16 weeks (P< 0. 05). Conclusions A single high-dose intraperitoneal injection of streptozotocin (150 mg/ kg) and five consecutive low-dose intraperitoneal injections of streptozotocin (50 mg/ kg) induced diabetic pulmonary fibrosis mouse models after 16 weeks of feeding, and both produced ideal animal models for diabetic pulmonary fibrosis.