Objective To compare differences in pulmonary vascular remodeling among chronic obstructive pulmonary disease (COPD) mouse models established via different method, cigarette smoke (CS) exposure, Klebsiella pneumoniae (KP) infection, and CS combined with KP (CS+KP), at different time points and to provide the basis for further study. Methods A total of 72 male mice were randomly divided into normal, CS, KP and CS+KP groups, with 18 per group. Mice in the CS group were exposed to cigarette smoke (3000±500 ppm) twice per day. KP was dripped into the nasal cavities of mice in the KP group (5×109 CFU/ L, times/7 d). Mice in the CS+KP group were subjected to CS exposure and KP nasal administration. Stimulation was stopped at the end of week 8. The mice were observed until week 16 and sacrificed at the end of weeks 4, 8, and 16. Lung function, including 50% expiratory flow (EF50) and tidal volume (TV), was measured every 4 weeks. Pulmonary small-vessel structures, including wall thickness percentage (WT%), lumen area percentage (LA%), and wall area percentage (WA%), were assessed by lung histopathology. Vascular endothelial growth factor (VEGF) levels in lung tissue were detected by immunohistochemistry. Results Compared with the normal group, the CS group showed decreased TV from weeks 8 to 12, decreased EF50 from weeks 8 to 16, increased WT% from weeks 8 to 16, increased WA% and VEGF in week 8 only, and decreased LA% in week 8 only (P<0. 05). In the CS+KP group, TV decreased from weeks 4 to 12; EF50 decreased from weeks 8 to 16; WT%, WA%, and VEGF increased from weeks 4 to 12; and LA% decreased from weeks 4 to 16 (P<0. 05). In the KP group, lung function did not change significantly, WT% increased only in week 8, and LA% decreased only in week 8 (P<0. 05). Compared with the CS group, the CS+KP group showed increased WT% and VEGF from weeks 8 to 16, increased WA% in week 16, and decreased LA% in week 16 (P<0. 05). Compared with the KP group, the CS+KP group showed increased WT%, WA%, and VEGF from weeks 8 to 16 and decreased LA% from weeks 4 to 16 (P<0. 05). In the CS group, WT% increased in week 8, VEGF increased in week 16, while LA% decreased in week 8 (P<0. 05). Conclusions Mice in the CS, KP, and combination groups had significant pathological COPD characteristics, including alveolar destruction, inflammatory infiltration, and pulmonary vascular remodeling, but each had its own characteristics. In the CS group, lung function decreased, and alveolar structure showed destruction and thickening in week 8 and were still observed in week 16, while pulmonary vascular remodeling was only observed in week 8. In the KP group, lung function did not decrease significantly, inflammatory infiltration was evident and persistent in lung tissue, but alveolar structure destruction and pulmonary vascular remodeling were only observed in week 8. In the CS+KP group, lung function decreased and alveolar structure destruction and pulmonary vascular remodeling were observed in week 4 and were still observable in week 16.