〔Abstract〕 Objective To explore the effect of ephedrine on airway remodeling and its regulation effect on transforming growth factor-β1(TGF-β1)/Smads pathway in asthmatic mice. Methods All mice were randomly separated into control group, model group, dexamethasone group, ephedrine low-dose group, ephedrine high-dose group, and ephedrine high-dose+TGF-β1 activator group, with 12 mice in each group. Except for the control group, mice in other groups were intraperitoneally injected with 40 μg ovalbumin(OVA) and 2 mg 10% aluminium hydroxide sensitizer to induce asthma models. After 8 weeks, the airway hyperresponsiveness of mice in each group was detected; eosinophils in bronchoalveolar lavage fluid(BALF) were counted; ELISA was applied to detect the levels of interleukin(IL)-4, IL-5, and IL-13 in BALF; hematoxylin-eosin(HE) staining and Masson staining were applied to observe the pathological changes and collagen fiber area of mouse lung tissue; immunohistochemistry was applied to detect the expression of α-smooth muscle actin(α-SMA) protein in mouse lung tissue; Western blot was applied to detect the expression of TGF-β1/Smads pathway related proteins in mouse lung tissue. Results Compared with the control group, the airway hyperreactivity at different doses of methacholine, total area of airway wall(Wat)/perimeter of the basement membrane(Pbm) ratio, collagen fiber area, eosinophil, the contents of IL-4, IL-5, IL-13, the expression of α-SMA, TGF-β1, the ratios of p-Smad2/Smad2 and p-Smad3/Smad3 in the model group increased(P<0.05), the expression of Smad7 decreased(P<0.05); compared with the model group, the airway hyperreactivity at different doses of methacholine, Wat/Pbm ratio, collagen fiber area, eosinophil, the contents of IL-4, IL-5, IL-13, the expression of α-SMA, TGF-β1, the ratios of p-Smad2/Smad2 and p-Smad3/Smad3 in the dexamethasone group, the ephedrine low-dose and high-dose groups decreased(P<0.05), the expression of Smad7 increased(P<0.05); compared with the ephedrine high-dose group, the airway hyperreactivity at different doses of methacholine, Wat/Pbm ratio, collagen fiber area, eosinophil, the contents of IL-4, IL-5, IL-13, the expression of α-SMA, TGF-β1, the ratios of p-Smad2/Smad2 and p-Smad3/Smad3 in the ephedrine high-dose+TGF-β1 activator group increased(P<0.05), the expression of Smad7 decreased(P<0.05). Conclusion Ephedrine can improve airway remodeling in asthmatic mice, and its mechanism is related to the regulation of TGF-β1/Smads signaling pathway.