Objective To investigate the relationship between the expression of leukocyte antigen DR (HLA‑DR) on monocytes and acute exacerbation of chronic obstructive pulmonary disease (COPD). Methods A total of 37 patients with acute exacerbation of COPD (AECOPD) who were admitted to Tianjin Nankai Hospital and healthy persons for physical examination were selected. According to their clinical symptoms and infection indicators, the patients were divided into three groups: a healthy control group (n=15), an acute group (n=22, before clinical treatment intervention) and a stable group (n=16, after clinical intervention). Their peripheral blood samples were collected, and the expression of HLA‑DR on CD14+ monocytes was detected by flow cytometry. Their relationships with C‑reactive protein (CRP), white blood cell count, neutrophil percentage, neutrophil count, CD3+ T lymphocyte percentage, CD3+CD4+ T lymphocyte percentage, CD3+CD8+ T lymphocyte percentage and CD4+/CD8+ were analyzed. Results Compared with the healthy control group, patients in the acute group showed remarkable decreases in the levels of HLA‑DR on CD14+ monocytes (P<0.05). Compared with the acute group, the stable group presented significant increases in the expression of HLA‑DR on CD14+ monocytes (P<0.05), decreases in CRP levels (P<0.05), white blood cell count, neutrophil percentage and neutrophil count (all P<0.05), and increases in CD3+CD4+ T cell percentage, and CD4+/CD8+ (all P<0.05). In contrast, no significant changes were found in the percentage of CD3+ T lymphocytes and the percentage of CD3+CD8+ T lymphocytes (all P>0.05). Correlation analysis indicated that, the expression of HLA‑DR on CD14+ monocytes in the peripheral venous blood of the acute group was negatively correlated with CRP, but positively correlated with the percentage of CD3+CD4+ T lymphocytes and CD4+/CD8+. Conclusions The expression of HLA‑DR on CD14+ monocytes in AECOPD patients is reduced, which can be used as an auxiliary indicator to evaluate the immune system.