Objective To investigate the effect and mechanism of verteporfin (Vp) in airway remodeling of experimental asthma. Methods (1) Animal experiment: Twelve female BALB/c mice were divided into 3 groups (4 each): control group experimental asthma group and Vp intervention asthma group. Mice in experimental asthma group were treated by intranasal delivery of house dust mite (HDM) extract, in Vp intervention group were treated with intraperitoneal injection of Vp before HDM stimulation, and in control group was treated with the same amount of normal saline. Lung tissues and bronchoalveolar lavage fluid (BALF) of mice were collected, HE staining, Masson staining and Periodic Acid-Schiff (PAS) staining were used to observe the pathological changes of lung tissue, Wright-Giemsa staining was used to count the inflammatory cells in BALF, and the expressions of Yes-associated protein (YAP) and phosphorylated Yes-associated protein (p-YAP) in lung tissues were detected with immunohistochemistry, RT-PCR and Western blotting were performed to detect the expressions of YAP, p-YAP, osteopontin (OPN)and smooth muscle myosin heavy chain (SMMHC). (2) Cell experiment: Human airway smooth muscle cells (HASMC) were divided into control group (treated with the same amount of normal saline), HDM group (treated with 50 μg/ml HDM for 24 hours)and HDM+Vp group (treated with 0.05 mg/L Vp for 2 hours, and then with 50 μg/ml HDM for 24 hours). The cell proliferation of HASMC was detected by CCK-8. The apoptosis rate of HASMC were detected by flow cytometry. The protein levels of YAP, OPN and SMMHC in cells were detected by Western blotting. Results (1) Animal experiment: Compared with control group, the lung inflammation was aggravated, the bronchial basement membrane, airway smooth muscle (ASM) and airway wall were thickened in experimental asthma group [(1.13±0.38) μm vs. (0.79±0.36) μm, (6.49±2.36) μm vs. (4.56±1.52) μm, (33.85±5.95) μm vs. (22.08±3.30) μm, P<0.05]. The deposition proportion of collagen fiber around airway and PAS staining area increased(5.85%±2.35% vs. 0.36%±0.12%, 28.81%±5.89% vs. 13.57%±2.08%, P<0.01). The mRNA and protein expression levels of YAP and OPN increased (P<0.05 or P<0.01), and the ratio of p-YAP/YAP and the mRNA and protein expression levels of SMMHC decreased (P<0.05 or P<0.01). Compared with experimental asthma group, the lung inflammation was reduced, and the thickness of bronchial basement membrane, ASM and airway wall were thinned in Vp intervention group [(0.93±0.27) μm, (4.99±1.75) μm,(26.59±2.76) μm, P<0.05]. The deposition proportion of collagen fiber around airway and PAS staining area decreased obviously(2.14%±0.89%, 17.92%±1.89%, P<0.05). The mRNA and protein expression levels of YAP and OPN decreased markedly (P<0.05 or P<0.01), and the ratio of p-YAP/YAP and the mRNA and protein expression levels of SMMHC increased (P<0.05). (2) Cell experiment: Compared with control group, the cell proliferation ability was higher (0.2874±0.0055 vs. 0.2626±0.0051, P<0.01)and apoptosis rate was lower in HDM group (5.14%±0.82% vs. 6.75%±0.21%, P<0.05). The protein expressions of YAP and OPN increased (3.14±0.48 vs. 1.51±0.61, 5.87±2.42 vs. 0.94±0.23, P<0.01), while of SMMHC decreased (0.80±0.19 vs. 2.96±0.96,P<0.01). Compared with HDM group, the cell proliferation ability reduced (0.2748±0.0043, P<0.05) and apoptosis rate increased(6.29%±0.49%, P<0.05), the protein expressions of YAP and OPN decreased (2.02±0.53, 2.93±1.09, P<0.05), while of SMMHC increased (2.11±0.85, P<0.05) in HDM+Vp group. Conclusions The abnormal expression of YAP may be involved in the airway remodeling in experimental asthma, and Vp may restrain the airway remodeling in experimental asthma by decreasing the YAP activity and nuclear shift, and reversing the HASMC phenotypic transformation.