〔Abstract〕 Objective To investigate the efficacy of dihydroxypropylline combined with non-invasive sequential mechanical ventilation on acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated with respiratory failure and the effects on serum levels of hypersensitivity C-reactive protein (hs-CRP), γ-glutamyl transferase (GGT) and cysteine protease inhibitor C (CysC). Methods 80 patients with AECOPD complicated with respiratory failure admitted to the 988th Hospital of the Joint Logistic Support Force from February 2020 to December 2022 were randomly divided into an observation group and a control group, with 40 cases in each group. The control group was treated with non-invasive sequential mechanical ventilation, while the observation group was treated with dihydroxyprophylline combined with non-invasive sequential mechanical ventilation. The clinical efficacy, changes in blood gas indexes and lung function before and 7 days after treatment were compared between the two groups, and the changes in the levels of hs-CRP, GGT and CysC were compared between the two groups. Results The total effective rate of the observation group was significantly higher than that of the control group, the difference was statistically significant (P < 0.05). After treatment, arterial partial pressure of oxygen (PaO₂) was increased and arterial partial pressure of carbon dioxide (PaCO₂) was decreased in the two groups. After treatment, the level of PaO₂ in the observation group was higher than that in the control group and the level of PaCO₂ was lower than that in the control group, with statistical significance (P < 0.05). After treatment, the levels of forced expiratory volume in one second as percentage of predicted volume (FEV1%pred), forced vital capacity as percentage of predicted volume (FVC%pred) and forced expiratory volume in one second/forced vital capacity (FEV1/FVC) were increased in the two groups, and after treatment, the levels of FEV1%pred, FVC%pred and FEV1/FVC in the observation group were higher than those in the control group, the differences were statistically significant (P < 0.05). After treatment, the levels of hs-CRP, GGT and CysC in the two groups were decreased, and the levels of hs-CRP, GGT and CysC in the observation group were lower than those in the control group, the differences were statistically significant (P < 0.05). Conclusion Dihydroxyprophylline combined with non-invasive sequential mechanical ventilation can improve the clinical therapeutic effect of AECOPD patients with respiratory failure, improve blood gas indexes, enhance lung function, reduce disease severity and inflammatory response levels.