Chronic Obstructive Pulmonary Disease (COPD) is one of the leading causes of death worldwide, and current treatments fail to significantly halt its progression. Exosomes derived from mesenchymal stem cells (MSCs-Exos) have demonstrated promising potential in treating COPD due to their anti-inflammatory and regenerative biological properties. In this study, we investigated the potential anti-inflammatory effects of bone marrow mesenchymal stem cell-derived exosomes (BMSCs-Exos) in a COPD rat model and the possible mechanisms by which they inhibit airway remodeling, as well as identifying the optimal dosage and administration route. Our results show that nebulized BMSC-Exos significantly improve lung function in COPD rats while reducing pulmonary inflammatory infiltration, bronchial mucus secretion, and collagen deposition. Moreover, BMSC-Exos treatment notably decreased the expression of pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1β, and the pro-fibrotic factor TGF-β1 in serum, bronchoalveolar lavage fluid (BALF), and lung tissue. The most pronounced therapeutic effect was observed at a low dose of exosomes. Furthermore, quantitative real-time PCR and immunohistochemical analyses revealed that nebulized BMSC-Exos significantly inhibited airway remodeling and epithelial-mesenchymal transition (EMT) by suppressing the Wnt/β-catenin signaling pathway. In conclusion, these findings indicate that nebulized BMSC-Exos offer a noninvasive therapeutic strategy for COPD by mitigating lung inflammation and airway remodeling through the suppression of abnormal Wnt/β-catenin pathway activation induced by cigarette smoke (CS) and lipopolysaccharide (LPS) in rats.