Objective To investigate the effects of melatonin(MEL) on pulmonary artery pressure and expression of cyclooxygenase-2 (COX-2) in rats with monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Methods Thirty-six rats were randomly divided into control group, model group (MCT), and intervention group (MCT+MEL). MCT of 2.5ml/kg (50mg/kg, dissolved in mixture of anhydrous ethanol and normal saline) was injected intraperitoneally into the rats of the model group and intervention group to establish PAH. The rats from the control group received intraperitoneal injection of 2.5ml/kg of the solvent. From the 1st day to the 28th day after the injection, MEL of 10ml/kg (10mg/kg, dissolved in mixture of anhydrous ethanol and normal saline) was injected intraperitoneally in the intervention group, once a day, and the control group and the model group were given same dose of the solvent. Mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI), vascular wall thickness/vascular external diameter (WT%), vascular wall area/total vascular area(WA%), and the average optical density(AOD) of COX-2 expression were measured and recorded. SPSS statistics 22.0 was used for data analysis. Results Compared with control group, the mPAP, RVHI, WT%, WA% and AOD were significantly higher in the model group, but the above indices were reduced in the intervention group when compared with those of the model group, but still higher than those in control group with statistical significance (P<0.001). Correlation analysis showed that AOD was positively correlated with mPAP, RVHIV, WT% and WA% (r=0.836,0.749,0.823,0.821 respectively, P<0.01). Conclusion MEL can reduce MCT-induced PAH and improve pulmonary vascular remodeling in rats, which may be associated with its inhibiting COX-2 expression.