In the present study, the clinical efficacy of the immune modulator lentinan combined with inhalation of the corticosteroid budesonide in treating acute exacerbation of chronic obstructive pulmonary disease (AECOPD) under mechanical ventilation was assessed. A total of 72 cases of AECOPD treated at Shanghai Jiao Tong University Affiliated Sixth People's Hospital (Shanghai, China) between June 2016 and September 2017 were enrolled. The AECOPD patients were randomly divided into an experimental group (n=36) and a control group (n=36). All of the patients received ventilator support and endotracheal intubation was performed. The experimental group was orally administered lentinan and budesonide was administered via atomization inhalation through a Y-tube and the control group received only budesonide via Y-tube. After the treatment, airway pressure, the time of mechanical ventilation and the time of stay at the intensive care unit for the experimental group were significantly lower than those for the control group (P<0.001). The plasma levels of adiponectin, D-dimer, interleukin-17 and high-sensitivity C-reactive protein, as well as the pressure of CO 2 in the experimental group were significantly lower than those in control group (P<0.001). Furthermore, the partial O 2 pressure in the experimental group was significantly higher than that in the control group (P<0.001). After the combined treatment, the proportions of CD3 + and CD4 +T-cells in the blood were elevated, while the proportion of CD8 +T-cells was decreased, compared with those in the experimental group at baseline or the control group post-treatment. In conclusion, the strategy of lentinan treatment combined with budesonide inhalation for AECOPD patients under mechanical ventilation demonstrated improved clinical efficacy compared with budesonide alone. (Chinese Clinical Trial Registry no. ChiCTR1800019088).