Pulmonary arterial hypertension (PAH) is characterised by increasing pulmonary pressure, right ventricular failure, and death. The typical pathological changes include medial hypertrophy, intimal fibrosis and in situ thrombosis. 5-HT and other factors contributed to the development of pathologic lesions. Aspirin (ASA), the platelet aggregation inhibitor, inhibits 5-HT release from platelet. The aim of the current study was to determine the efficacy of aspirin in preventing or attenuating pulmonary hypertension. Sprague-Dawley (SD) rats injected with monocrotaline (MCT) at day 0 developed severe PAH at day 31. Rats were randomised to receive either vehicle or different dosages of aspirin (ASA 0.5 mg/kg/d, ASA 1 mg/kg/d, ASA 2 mg/kg/d, ASA 4 mg/kg/d). Aspirin suppressed PAH and increased survival rate compared with the placebo group (84% vs 60%, p<0.05). Aspirin treatment also reduced right ventricular hypertrophy and pulmonary arterioles proliferation. Plasma 5-HT measured by High Performance Liquid Chromatographic (HPLC) was decreased in aspirin treated PAH model. The degree of 5-HT reduction was associated with systolic pulmonary arterial pressure, right ventricular hypertrophy and wall thickness of pulmonary arterioles in rats. These results showed ASA treatment has effectively attenuated MCT-induced pulmonary hypertension, right ventricular hypertrophy and occlusion of pulmonary artery. The effects of ASA may be associated with reduction of 5-HT.