Objective To establish rat models of chronic obstructive pulmonary disease (COPD) with smoking, protease instillation and smoking + protease instillation, and to evaluate and compare inflammation, imaging and pathology between these groups. Methods Rat models of COPD were established with smoking, protease instillation and smoking + protease instillation. There were 60 rats in the smoking group, 30 rats in the protease group and 30 rats in the smoking + protease group. The control group contained 20 rats. Body weight was measured every week. In the smoking and control groups, five and two rats were euthanized, respectively at 24 h, and weeks 1, 2, 4, 8, 12, 16, 20 and 24 during the modeling process, and in the protease and smoking + protease groups, five rats were euthanized in each group at 24 h, and weeks 1, 2, 4, 8 and 12. Rat lung tissues subjected to cytokine detection, micro-CT examination and pathological examination. Results The weight gain of rats in the smoking and smoking + protease group was significantly slower than the control group at week 7 (P< 0. 05). The levels of IL-10 at 24 h, and weeks 1, 2 and 4 were significantly lower in the protease group and the smoking + protease group compared with the control group (P< 0. 05). The concentration of MMP-9 at 24 h was significantly higher in the protease group and the smoking + protease group than the control group (P< 0. 05). Emphysema was observed on the micro-CT images and pathological images in the protease group and smoking + protease group at week 4, and in the smoking group at week 8. Conclusions Rat models of COPD can be successfully established by smoking, protease instillation and smoking + protease instillation. Micro-CT reflects changes in lungs with high sensitivity and validity.