Abstract: Objective To investigate the effect of acupuncture on TGF-β1/Smads signaling pathway in the lung tissue of mice with airway remodeling. Methods Thirty specific pathogen-free mice were randomly divided into blank group, model group and acupuncture group (n=10). Mouse models of asthma were established in the model group and the acupuncture group, and the mice in the latter group received 7 acupuncture therapies (at bilateral Fei Shu, Da Zhui and Zu Sanli, 20 min each time) every other day, starting on the 10th day after the modeling. At 24 h after the last acupuncture, the mice were subjected to inhalation of 1% OVA for 3 days, and 24 h after the last challenge, the mice were given methacholine chloride (Mch) inhalation at different concentrations for measurement of lung resistance using a noninvasive stroke volume meter. HE staining was used to observe the pathological changes in the lung tissues, and TGF-β1 levels in the the bronchoalveolar lavage fluid (BALF) and serum were detected using ELISA; Western blotting was used to detect the differential protein expressions in the airway smooth muscles between the two groups. The airway smooth muscle cells were isolated from the mice in the acupuncture group and treated with a TGF- β1 inhibitor (LY2157299), and the relative expressions of type- I and Smads proteins were detected using Western blotting. Results The mice in the model showed obvious tracheal fistula with airway pathologies including lumen narrowing, bronchial mucosa thickening, dissociation of the epithelial cells, and thickening of the alveolar septum and airway smooth muscles. These pathological changes were obviously milder in the acupuncture group. The asthmatic mice exhibited significantly increased lung resistance in positive correlation with Mch concentration. Serum TGF-β1 level was significantly elevated in asthmatic mice (P<0.05); TGF-β1 levels in the serum and BALF were significantly lower in the acupuncture group than in the model group (P<0.05). In the model group, the expressions of α-SMA, TGF-β1 and Smads in the airway smooth muscles were significantly higher than those in the other two groups (both P<0.05). In cultured airway smooth muscle cells, the expressions of type-I and Smads were significantly higher in cells treated with LY2157299 than in the control cells (P>0.05). Conclusion Acupuncture can inhibit airway remodeling by inhibiting the expression of airway TGF-β1 and down-regulating the expression of Smads and α-SMA to reduce airway inflammatory response. Airway expressions of type-I and Smads proteins remain high after inhibiting TGF-β1. Acupuncture may control asthma progression through the TGF-β1/Smads pathway.