Endoplasmic reticulum (ER) has been reported to be implicated in numerous pathologic conditions. However, little is known concerning the role of ER stress in the pathogenesis of bronchial asthma, particularly airway remodeling. We used a long-term exposure murine model of allergic airway disease to evaluate the effect of 4-PBA, an ER stress regulator, on hyperresponsiveness, inflammation, and remodeling of the airways. This study with the chronic model of allergic airway disease revealed the typical pathophysiological features; increased the expression of ER stress markers and the protein levels of unfolded- protein response (UPR)-related markers in lung tissues, increased numbers of airway inflammatory cells, increased plasma exudation, airway hyperresponsiveness, and increased levels of Th2 cytokines, TGF-β1, and vascular endothelial growth factor (VEGF). In addition, the mice chronically exposed to ovalbumin (OVA) developed features of airway remodeling, including thickening of the peribronchial smooth muscle layer, subepithelial collagen deposition, and increased airway mucus production. Administration of 4-PBA reduced the pathophysiological symptoms of asthma including airway remodeling, plasma exudation, Th2 cytokines, TGF-β1, and VEGF in lungs as well as the increased expression of ER stress markers and the protein levels of UPR-related markers after OVA inhalation. These results indicate that inhibition of ER stress may attenuate chronic antigen-induced airway inflammation, hyperresponsiveness, and airway remodeling.Endoplasmic reticulum (ER) has been reported to be implicated in numerous pathologic conditions. However, little is known concerning the role of ER stress in the pathogenesis of bronchial asthma, particularly airway remodeling. We used a long-term exposure murine model of allergic airway disease to evaluate the effect of 4-PBA, an ER stress regulator, on hyperresponsiveness, inflammation, and remodeling of the airways. This study with the chronic model of allergic airway disease revealed the typical pathophysiological features; increased the expression of ER stress markers and the protein levels of unfolded- protein response (UPR)-related markers in lung tissues, increased numbers of airway inflammatory cells, increased plasma exudation, airway hyperresponsiveness, and increased levels of Th2 cytokines, TGF-β1, and vascular endothelial growth factor (VEGF). In addition, the mice chronically exposed to ovalbumin (OVA) developed features of airway remodeling, including thickening of the peribronchial smooth muscle layer, subepithelial collagen deposition, and increased airway mucus production. Administration of 4-PBA reduced the pathophysiological symptoms of asthma including airway remodeling, plasma exudation, Th2 cytokines, TGF-β1, and VEGF in lungs as well as the increased expression of ER stress markers and the protein levels of UPR-related markers after OVA inhalation. These results indicate that inhibition of ER stress may attenuate chronic antigen-induced airway inflammation, hyperresponsiveness, and airway remodeling.