Objective To compare the effects and characteristics of cigarette smoke exposure (CSE) alone and CSE combined with airway instillation of bacterial lipopolysaccharide (LPS) in chronic obstructive pulmonary disease (COPD).Methods Male SD rats were randomly divided into control, CSE, and CSE+LPS groups, with 10 rats in each group. After 24 weeks, the models were established and the lung function of the rats was measured. Hematoxylin-eosin (HE) staining was performed to observe the pathological changes in the airway and lung tissue. The ELISA method was used to detect the level of serum interleukin-8 (IL-8) and tumor necrosis factor α (TNF-α) in peripheral blood.Results Airway resistance (RI), functional residual capacity (FRC), and chord compliance (Cchord) of the CSE and LPS+CSE groups were higher than those of the control group (all P < 0.05), while the tidal volume (TV), minute volume (MV), and forced expiratory volume in 50 ms (FEV50) / forced vital capacity (FVC) of the CSE and LPS+CSE groups were lower than those of the control group (all P < 0.05). HE staining of lung tissue showed that the average alveolar intercept and thickness of the small airway walls were higher in the CSE and LPS+CSE groups than those in the control group. Compensatory enlargement was evident in the alveolar cavity of the CSE and CSE+LPS groups, and the alveolar septum widened, with a fusion of pulmonary alveoli in the CSE+LPS group. The levels of IL-8 and TNF-α in serum of the CSE and CSE+LPS groups were higher than those of the control group (all P < 0.05). The level of TNF-α in serum of the CSE+LPS group was higher than that of the CSE group (P < 0.05).Conclusion The CSE combined with LPS method is superior to CSE alone for establishing the COPD rat model, and the combined model is closer to clinical manifestations.