Objective：To investigate the correlation between peripheral blood alpha 2 macroglobulin（A2M）and immune cell infiltration in patients with chronic obstructive pulmonary disease（COPD）. Methods：Comprehensive analysis of the GSE38974 dataset was performed. GO enrichment，KEGG analysis，and GSVA analysis were used to explore potential functions and pathways. CIBERSORT was used to assess tissue- infiltrating immune cells. Peripheral blood A2M levels and immune cell counts were analyzed in 25 stable COPD patients and 26 healthy controls. ELISA was used to detect the concentration of A2M in plasma. RT-qPCR was used to measure A2M mRNA expression levels in cells and peripheral blood. Western blot was used to measure the expression levels of the M2 macrophage surface marker arginase-1（Arg-1）. Pearson correlation analysis was used for correlation analysis. ROC curve was used to determine the diagnostic sensitivity and specificity of A2M. Results：Bioinformatics analysis of differentially expressed genes in GSE38974 dataset revealed that A2M expression was decreased in lung tissue of COPD patients and was correlated with immune cell infiltration in lung tissues of COPD patient. RT-qPCR and ELISA results showed that A2M levels were down-regulated in peripheral blood of COPD patients，and were correlated with lymphocytes and monocytes in COPD patients. ROC curve analysis showed that A2M had a diagnostic value for COPD. Further pathway analysis suggested that A2M might be associated with macrophages and other regulatory immune pathways. Knocking down of A2M in M2 macrophages resulted in decreased expression of Arg-1. Conclusion：The expression of A2M is decreased in lung tissue and peripheral blood of COPD patients and is closely related to the immune cell counts and immune cell infiltration in COPD patients. A2M may play an important role in the polarization of macrophages to the M2 phenotype.