Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by elevated pulmonary artery pressure, right ventricular (RV) hypertrophy, and vascular remodeling. Transforming growth factor-β-induced protein (TGFBI) is an extracellular matrix protein regulated by TGF-β that plays a critical role in pulmonary vascular remodeling in PAH. Here, we investigated the role of TGFBI in monocrotaline-induced PAH pathogenesis and evaluated the therapeutic effects of the endothelin receptor antagonist bosentan. Monocrotaline administration resulted in marked RV hypertrophy and increased medial wall thickness of pulmonary arterioles, accompanied by elevated TGFBI expression in both pulmonary vasculature and serum. Notably, bosentan treatment effectively reversed these pathological changes. In lung tissue, PAH induced upregulation of TGF-β1 and enhanced SMAD2/3 phosphorylation, both of which were normalized by bosentan. While TGFBI expression exhibited variable patterns in the heart, liver, and kidneys, TGF-β signaling alterations were predominantly observed in the lungs. Additionally, PAH promoted endothelial-to-mesenchymal transition (EndMT) in lung tissue, as evidenced by decreased expression of endothelial markers (CD31 and VE-cadherin) and increased expression of mesenchymal markers (Endothelin 1, COL1A1, COL3A1, SLUG, and Snail). Bosentan treatment effectively reversed these EndMT-related changes. Collectively, these findings highlight a critical role for TGFBI and TGF-β signaling in pulmonary vascular remodeling during PAH development, primarily through modulation of EndMT. This study suggests that targeting TGFBI may represent a promising therapeutic strategy for PAH management.