Chronic allergic asthma leads to airway remodeling and subepithelial fibrosis via mechanisms not fully understood. Airway remodeling is amplified by pro-fibrotic mediators, such as TGF-β1, which plays a cardinal role in various models of fibrosis. We recently have identified a critical role for JNK1 in augmenting the pro-fibrotic effects of TGF-β1, linked to epithelial to mesenchymal transition of airway epithelial cells. To examine the role of JNK1 in HDM-induced airway remodeling, we induced allergic airway inflammation in WT and JNK1-/- mice by administration of HDM extract. WT and JNK1-/- mice were sensitized with intranasal aspirations of HDM extract for 15 days over three weeks. HDM caused similar increases in airway hyperresponsiveness, mucus metaplasia and airway inflammation in WT and JNK1-/- mice. In addition, the pro-fibrotic cytokine TGF-β1 and phosphorylation of Smad3 were equally increased in WT and JNK1-/- mice. In contrast, increases in collagen content in lung tissue induced by HDM were significantly attenuated in JNK1-/- mice compared to WT controls. Furthermore HDM-induced increases of α-SMA protein and mRNA expression as well as the mesenchymal markers HMGA2 and collagen1A1 in WT mice were attenuated in JNK1-/- mice. The let7 family of microRNAs has previously been linked to fibrosis. HDM exposure in WT mice and primary lung epithelial cells resulted in striking decreases in let-7g miRNA that were not observed in mice or primary lung epithelial cells lacking JNK1-/- mice. Overexpression of let-7g in lung epithelial cells reversed the HDM-induced increases in α-SMA. Collectively, these findings demonstrate an important requirement for JNK1 in promoting HDM- induced fibrotic airway remodeling.