This study employs proteomics to explore key proteins implicated in pulmonary arterial hypertension (PAH) using a rat model. Our experimental design involved six male Sprague-Dawley (SD) rats aged 7-8 weeks, divided randomly into a control and a surgical group. The surgical group underwent a procedure to create a shunt between the abdominal aorta and the inferior vena cava, simulating high pulmonary blood flow, a characteristic condition of PAH. After 11 weeks, we assessed the success of our PAH model through transthoracic right heart catheterization, anatomical observations, and measurements of the right ventricular hypertrophy index. Proteomic analysis was conducted on the pulmonary artery tissues from the high-flow model rats, revealing differential protein expressions. We identified 137 upregulated proteins and 29 downregulated proteins. Our protein-protein interaction analysis highlighted significant changes, notably the upregulation of Arf6 and Vamp3 genes and the downregulation of the Rabif gene. These findings were validated through Western blotting. Using Tandem Mass Tags (TMT) for in vitro labeling, we successfully analyzed protein interactions under high pulmonary blood flow conditions. This study not only elucidates the proteomic alterations associated with PAH but also provides potential genomic targets for clinical interventions. The identified proteins and gene interactions offer new directions for therapeutic strategies in treating PAH, suggesting a promising avenue for future research and clinical applications.