To investigate the significance of the presence or absence of the thymus in the development of pulmonary hypertension (PH) following monocrotaline (MCT) administration, the degree of MCT-induced PH (MCT-PH) in athymic nude (F344/N Jcl-rnu) rats was compared with that in their euthymic (rnu/+) littermates. Histopathological studies of the lung in terms of interstitial edema, congestion, thickening of the alveolar wall, inflammatory cell infiltration and degeneration of arteries were performed by staining with hematoxylin-eosin (HE), elastin van Gieson and Masson’s trichrome. The medial wall thickness of the small pulmonary arteries and the weight ratio of the right ventricular free wall (RV) to that of the left ventricle plus septum [RV/(LV+ S) weight ratio] were used as indices of the degree of PH. Toluidine blue staining was performed to estimate the number of the mast cells in the lung interstitium. Interstitial edema was significantly severer in MCT-injected euthymic rats than in MCT-injected athymic nude rats (p< 0.01); in contrast, the thickening of the alveolar wall was severer in MCT-injected athymic nude rats than in MCT-injected euthymic rats (p< 0.05). The degree of MCT-PH, as determined by the medial wall thickness of the small pulmonary arteries and RV/(LV+ S) weight ratio in MCT-injected athymic nude rats, was significantly severer than in MCT-injected euthymic rats (p< 0.05 and p< 0.01, respectively). The number of mast cells was significantly greater in MCT-injected athymic nude rats than in MCT-injected euthymic rats (p< 0.01). The degree of the medial wall thickness of the small pulmonary arteries was significantly correlated with RV/(LV+ S) weight ratio (p< 0.05) as well as with the number of mast cells in MCT-injected rats. Athymic nude rats developed severer PH than euthymic rats along with a greater number of mast cells and severer histopathological changes, such as thickening of the alveolar wall. Mast cell proliferation was considered to play a pivotal role in the development of PH in MCT-PH.