Asthma is a complicated systemic disease of the airways, which is characterized by variable symptoms, including bronchial hyper-responsive-ness, inflammation and airflow obstruction. The prevalence of asthma has increased 2-3-fold over recent decades in developed countries; however, the molecular mechanism of asthma remains unclear. In the current study, the expression of recombinant protein Dermatophagoides farinaeI (Derf I) was induced by isopropyl beta-D-1-thiogalactoside (IPTG) and purified using Ni-NTA. Derf I, an important antigen of asthma, was used to establish the animal model of asthma. Airway hyper-responsiveness was mea-sured using unrestrained whole-body plethysmography with a four-chamber system. Immunoglobulin (Ig) E, IgG and IgG2a were analyzed using indirect enzyme-linked immunosorbent assay (ELISA). Proteomic technology was applied to detect the difference between the normal lung tissue and asthma lung tissue samples of the asthma model. Cytokines in bronchoalveolar lavage fluid and the splenocyte culture medium were measured by ELISA and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect the mRNA expression of ATP synthase, H+ transporting, mitochondrial F1 complex, beta polypeptide (ATP5b). In addition, cell growth of arterial smooth muscle cells (ASMCs) was evaluated by MTT assay. In the current study, Derf I was successfully used to construct the animal model of asthma. Out of 23 proteins that exhibit 3-fold upregulation or downregulation, ATP5b was chosen for further investigation. The data indicated that ATP5b was overexpressed in the asthma lung tissue when compared with the normal lung tissue. However, when ATP5b was knocked down, cell growth decreased. Therefore, overexpressed ATP5b leads to airway smooth muscle cell (ASMC) proliferation and finally to ASM thickening. Thus, to the best of our knowledge, this is the first study to report that the expression level of ATP5b was markedly increased in lung tissue samples of an asthma model compared with the tissue samples from normal lungs, which promoted ASMC proliferation and contributed to airway remodeling.