Background <p>Chronic obstructive pulmonary disease (COPD) is a common disease with respiratory symptoms and limited airflow. Exosomes derived from Tregs (Treg-exo) could regulate immune function and prevent autoimmune disease. This study assessed Treg-exo effects on COPD.</p> Methods <p>In vivo, rats were divided into three groups including control, COPD and exosomes groups. COPD models were established by passive smoking combined with lipopolysaccharide. Phosphate buffered saline or Treg-exo were administered via tail vein. Lung function, Hematoxylin and Eosin staining, and enzyme-linked immunosorbent assay (ELISA) were performed to evaluate lung function, histopathology and inflammation. Flow cytometry was used for peripheral blood T cell separation and counting. In vitro, COPD cluster of differentiation (CD) 4⁺ T-cells were isolated from spleen and co-cultured with Treg-exo alone or in combination with Colivelin (a signal transducer and activator of transcription 3/STAT3 activator). Flow cytometry, ELISA, and Western blot were used to count T helper cell 17 (Th17) and detected cytokines and STAT3 proteins expression.</p> Results <p>In vivo, pulmonary function tests and HE staining showed Treg-exo treatment enhanced lung function and alleviated lung damage; flow cytometry showed Treg-exo treatment decreased CD8⁺, CD4⁺ CD25^- cells and Th17; ELISA assay found Treg-exo treatment increased transforming growth factor-β and interleukin (IL)-10 and decreased tumor necrosis factor-α and IL-8 in serum, broncho alveolar lavage fluid, and lung tissue. In vitro, Treg-exo treatment inhibited Th17 differentiation and suppressed the content of IL-6, IL-17, and IL-23 and STAT3 phosphorylation.</p> Conclusions <p>Treg-exo suppressed inflammation and CD4⁺ T-cell differentiation to Th17, possibly by inhibiting STAT3 phosphorylation.</p> Graphical abstract <p></p>