Aim To develop a reliable mouse model of pulmonary hypertension (PH) using monocrotaline (MCT). Methods Female C57BL/6 mice aged 6 to 8 weeks were selected and administered MCT through intraperitoneal injection once weekly for three weeks. On days 10, 20, and 30 after the final injection, the mice were evaluated. A 0.55×20 mm disposable infusion needle was inserted through the intercostal muscles to access the right ventricle, and the right ventricular systolic pressure (RVSP) was recorded with the Medlab biological signal acquisition system. The heart was dissected, the body weight (BW), right ventricle (RV), and left ventricle plus septum (LV+S) were measured, and then the right ventricular hypertrophy index (RVHI = RV/BW) and Fulton index (RV/LV+S) were calculated. Lung tissue sections were prepared for pathological analysis. Then, immunofluorescence (IF) staining was performed for hematoxylin-eosin (HE) and α-smooth muscle actin (α-SMA) to examine changes in pulmonary vascular structure. Results At each of the three time points, RVSP, RVHI, and RV/LV+S values in C57 mice were markedly higher than those in the control group. HE staining confirmed significant thickening of the pulmonary vascular walls, while IF staining revealed the expression levels of α-SMA proteins were significantly increased whereas the expression levels of CD31 proteins were significantly decreased. Conclusion Administering a consistent dose of MCT via weekly intraperitoneal injections for three weeks can create a stable mouse model of pulmonary hypertension over 30 days.