Background: Current therapeutic options of pulmonary hypertension remain unsatisfactory as a result of high cost, limited effectiveness, or serious side effects. The purpose of this study was to investigate the therapeutic effects of small hairpin RNA (shRNA) targeting endothelin-converting enzyme(ECE)-1 in monocrotaline (MCT)-induced pulmonary hypertensive rats. Methods: Sprague-Dawley rats were divided into three groups: control group, MCT group and shRNA group. To assess the effects of shRNA targeting ECE-1 on the time course, heart and lung were dissected on days 4, 7, 14, and 28. Mean right ventricular pressure (RVP) was estimated. Histopathologic examination, RT-PCR and western blot analyses of several genes and proteins were performed Results: The shRNA group showed a significant improvement of RVP compared to the MCT group. The mRNA expressions and the protein levels of vascular endothelial growth factor (VEGF), caspase 3, Bcl2, interleukine (IL)-6 and tomor necrosis factor (TNF) 慣 and aniotensin converting enzyme (ACE)of lung tissues and brain natriuretic peptide (BNP) and troponin I (Tn I) in heart tissues were significantly increased in the MCT group compared to the control group on days 14 and 28. The mRNA expressions or protein contents of TNF 慣 were significantly decreased in the shRNA group compared to the MCT group on days 14, 28. Protein contents of L-6, ACE was significantly decreased in the shRNA group compared to the MCT group on day 14. The mRNA expressions of VEGF were significantly decreased in the shRNA group compared to the MCT group on days 14 and 28. Conclusions: Recombinant lentiviral vectors carrying shRNA targeting ECE-1 significantly decreased VGEF and TNF 慣 gene expressions and decreased IL-6 and ACE protein contents. These findings suggest the possibility that this treatment modality could be effective on reduced the vessel remodeling and antiinflammory action in pulmonary hypertension.