Objective To investigate the effect of noninvasive ventilation combined with pulmonary rehabilitation therapy on pulmonary function and serum inflammatory factors in patients with chronic obstructive pulmonary disease (COPD) and hypercapnia. Methods A total of 102 patients with COPD and hypercapnia who were treated in the hospital from January 2020 to December 2022 were selected and randomly divided into the conventional treatment group (n=51) and the conventional treatment combined with pulmonary rehabilitation group (n=51) by the random number table method. The conventional treatment group was given noninvasive ventilation therapy on the basis of conventional treatment, and the conventional treatment combined with pulmonary rehabilitation group was given pulmonary rehabilitation therapy on the basis of the conventional treatment group. The two groups were compared on blood gas indicators ［partial pressure of carbon dioxide (PaCO2), partial pressure of oxygen (PaO2), blood oxygen saturation (SaO2)］, pulmonary function ［forced expiratory volume in the first second in percent predicted values ［FEV1(%pred)］, forced vital capacity in percent predicted values ［FVC(%pred)］, peak expiratory flow in percent predicted values ［PEF(%pred)］ and percent of forced vital capacity exhaled in the first second (FEV1/FVC%))］, inflammatory factors ［tumor necrosis fact-α (TNF-α), hypersensitive C-reactive protein (hs-CRP), interleukin-8 (IL-8)］ and immune function ［T lymphocyte subsets (CD3+, CD4+, CD3+/CD4v+ and CD4+/CD8+)］ were compared between the two groups of patients.Results After 4 weeks of treatment, the PaCO2, TNF-α, hs-CRP, IL-8 and CD3+/CD4+ in both groups decreased, and above indicators in the conventional treatment combined with pulmonary rehabilitation group were lower than those in the conventional treatment group (all P＜0.05). The PaO2, SaO2, FEV1(%pred), FVC(%pred), PEF(%pred), FEV1/FVC%, CD3+, CD4+ and CD4+/CD8+ were enhanced, and above indicators in the conventional treatment combined with pulmonary rehabilitation group were higher than those in the conventional treatment group (all P＜0.05). Conclusion Noninvasive ventilation combined with pulmonary rehabilitation therapy can improve the blood gas status and pulmonary function, reduce the levels of inflammatory factors and enhance the immune function in patients with COPD and hypercapnia