Purpose: Although estrogen receptors (ERs) signal pathways are involved in the pathogenesis and development of asthma, their expressions and effects remain controversial. This study aimed to investigate the expressions of ERa and ER beta as well as their mechanisms in airway remodeling and mucus production in asthma. Methods: The expressions of ER alpha and ER beta in the airway epithelial cells of bronchial biopsies and induced sputum cells were examined by immunohistochemistry. The associations of ERs expressions with airway inflammation and remodeling were evaluated in asthmatic patients. In vitro, the regulations of ERs expressions in human bronchial epithelial cell lines were examined using western blot analysis. The epidermal growth factor (EGF)-mediated ligand-ndependent activation of ER alpha and its effect on epithelial-mesenchymal transitions (EMTs) were investigated in asthmatic epithelial cells by western blot, immunofluorescent staining, and quantitative real-time polymerase chain reaction. Results: ER alpha and ER beta were expressed on both bronchial epithelial cells and induced sputum cells, and the expressions showed no sex difference. Compared to controls, male asthmatic patients had higher levels of ER alpha on the bronchial epithelium, and there were cell-specific expressions of ER alpha and ER beta in induced sputum. The expression of ER alpha in the airway epithelium was inversely correlated to forced expiratory volume in 1 second (FEV1) % and FEV1/forced vital capacity. Severe asthmatic patients had significantly greater levels of ER alpha in the airway epithelium than mild-moderate patients. ER alpha level was positively correlated with the thickness of the subepithelial basement membrane and airway epithelium. In vitro, co-stimulation of interleukin (IL)-4 and EGF increased the expression of ER alpha and promoted its nuclear translocation. EGF activated the phosphorylation of ER alpha via extracellular signalregulated kinase and c-Jun N-terminal kinase pathways. ER alpha knockdown alleviated EGF-mediated EMTs and mucus production in airway epithelial cells of asthma. Conclusions: ERa contributes to asthmatic airway remodeling and mucus production through the EGF-mediated ligand-independent pathway.