ObjectiveTo compare the efficacies of exposure to cigarette smoke alone and in combination with intra-tracheal injection of lipopolysaccharide in establishing rat models of chronic obstructive pulmonary disease (COPD). MethodsA total of 24 8-week-old healthy Wistar rats were randomly divided into 2 model groups and a control group (Group C). The rat COPD models were established by two ways: intratracheal injection of lipopolysaccharide (LPS) twice + exposure to cigarette smoke for 1 month (Group A), and cigarette smoke inhalation for 80 days only(Group B). The pathologic characteristics of animal models, including the mean lining interval (MLI) and the mean alveoli number(MAN), were determined. The total and different white blood cell counts in bronchoalveolar lavage fluid(BALF) and blood samples were determined.ResultsThe rats in the two model groups presented with cough or breathlessness periodically, and the white blood cell counts and neutrophil counts in the peripheral blood and BALF were significantly higher than those in the control group (P<0.01). H-E staining showed that the lung tissues of rats in Group A and B had typical pathological features of COPD and emphysema. MLI were significantly higher and MAN were significantly lower in Group A and B than those in group C (both P<0.01), but there was no statistical difference between the two model groups. Group A had more severe inflammatory response in the bronchial and lung tissues than Group B. And Group B was characterized by alveolar overdistension.ConclusionBoth the two methods can successfully establish rat COPD model, with its pathophysiological changes similar to those of human COPD, with intra-tracheal injection of lipopolysaccharide being more consistent to the natural development of disease.