Objective To explore the preventive and therapeutic effects of diminazene (DIZE) on pulmonary arterial hypertension (PAH) in rats. Methods Left pulmonary lobectomy combined with injection of monocrotaline was used to establish a rat model of pulmonary arterial hypertension. One hundred adult male Wistar rats were randomly divided into blank control group (group A, n=20), DIZE control group (group B, n=20), PAH model group (group C, n=20), PAH model plus DIZE group (group D, n=20) and PAH model plus DIZE and C-16 group (group E, n=20). Angiotensin-converting enzyme 2 (ACE2), IL-6 and IL-8 levels were determined by fluorescence resonance energy transfer (FRET) and enzyme linked immunosorbent assay (ELISA), and the mean pulmonary arterial pressure (mPAP) and right ventricular hypertrophy index (RVHI) were measured. The wall thickness (WT) and intimal hyperplasia score were calculated, and the pulmonary vascular lesions were analyzed using elastic fiber staining. Results RVHI, ACE2 enzyme activity and WT in the group A were significantly different from those of the groups C, D and E (P<0.05). Those of the group D and E were significantly different (P<0.05). The five groups showed significant differences in the overall analysis of each index (P<0.05). Conclusions Diminazene can increase the ACE2 enzyme activity, and decrease the mPAP, RVHI and WT, while reducing the pulmonary arterial medial hypertrophy, and inhibit intimal hyperplasia of pulmonary arterioles. The results of this study provide an experimental basis for the use of diminazene in the treatment of human pulmonary hypertension.