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Background: Stemona tuberosa has long been used in Korean and Chinese medicine to ameliorate various lung diseases such as pneumonia and bronchitis. However, it has not yet been proven that Stemona tuberosa has positive effects on lung inflammation. Methods: Stemona tuberosa extract (ST) was orally administered to C57BL/6 mice 2 hr before exposure to CS for 2 weeks. Twenty-four hours after the last CS exposure, mice were sacrificed to investigate the changes in the expression of cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), chemokines such as keratinocyte-derived chemokine (KC) and inflammatory cells such as macrophages, neutrophils, and lymphocytes from bronchoalveolar lavage fluid (BALF). Furthermore, we compared the effect of ST on lung tissue morphology between the fresh air, CS exposure, and ST treatment groups. Results: ST significantly decreased the numbers of total cells, macrophages, neutrophils, and lymphocytes in the BALF of mice that were exposed to CS. Additionally, ST reduced the levels of cytokines (TNF-alpha, IL-6) and the tested chemokine (KC) in BALF, as measured by enzyme-linked immunosorbent assay (ELISA). We also estimated the mean alveolar airspace (MAA) via morphometric analysis of lung tissues stained with hematoxylin and eosin (H&E). We found that ST inhibited the alveolar airspace enlargement induced by CS exposure. Furthermore, we observed that the lung tissues of mice treated with ST showed ameliorated epithelial hyperplasia of the bronchioles compared with those of mice exposed only to CS. Conclusions: These results indicate that Stemona tuberosa has significant effects on lung inflammation in a subacute CS-induced mouse model. According to these outcomes, Stemona tuberosa may represent a novel therapeutic herb for the treatment of lung diseases including COPD.