Abstract: AIM: To explore the effect of simvastatin, an inhibitor of HMG-COA, on the expression of cyclooxygenase-2 (COX-2) in a rat model of pulmonary artery hypertension (PAH). METHODS: Thirty male Sprague Dawley rats were randomized into three groups equally: control group, PAH model group and treatment group with intervention of simvastatin. Changes of mean pulmonary arterial pressure (mPAP), endomembrane proliferation in the pneumono-arteriole and the average vascular occlusion scores (VOS) were measured. Gene and protein expression of COX-2 were also measured, respectively, by fluorescent quantitation PCR and immunohistochemistry. RESULTS: mPAP, pneumono-arteriole and VOS increased significantly in the PAH model group compared with those in the control group (P<0.05). Expression of COX-2 both at the level of gene and protein was significantly higher in the PAH model group than in the control group (P<0.05). With the intervention of simvastatin, mPAP and endomembrane proliferation in the pneumono-arteriole and VOS decreased dramatically (P<0.05) compared with those in the model group (P<0.05). CONCLUSION: PAH model has been induced successfully by pneumonoresection+monocrotaline (MCT) and simvastatin may hamper PAH partly by inhibiting the expression of COX-2 in pulmonary artery.