The aim of this study is to investigate the effects of RNA interference (RNAi) targeting angioten-sin 1a receptor (AT1a) on blood pressure and cardiac hypertrophy of rats with renovascular hypertension. Two RNAi plasmids, pAT1a-shRNA1 and pAT1a-shRNA2 each carrying a U6 promoter and an AT1a-specific shRNA-coding template sequence corresponding to the sites 928-946, 978-996 of the mRNA transcript, and a control plasmid pCon carrying a nonspecific shRNA-coding sequence were constructed. Thirty Sprague - Dawley rats with renovascular hypertension (2-kidney 1-clip) were randomly divided into 5 equal groups: Control group (without any intervention), pAT1a-shRNA1, pAT1a-shRNA2, pCon groups (with injection of the corresponding plasmid 4 mg/kg respect-d-1 by gavage). Three weeks after drug administration, pAT1a-shRNA1, pAT1a-shRNA2 and valsartan respectively resulted in decrease of the tail blood pressure by (15.1±5.4), (16.4±8.4) and (30.6±18.2) mmHg. However, the tail blood pressure increased further by about 25 mmHg in both of pCon and control groups. The carotid artery pressures of pAT1a-shRNA1, pAT1a-shRNA2 and valsartan groups were all significantly lower than those of the control and pCon groups. The ratio of left ventricle weight to body weight (LV/BW) of the rats in pAT1a-shRNA1, pAT1a-shRNA2, and val-sartan groups decreased significantly than in the control group (P0.05). Histopathological examination showed that the myocardiocytes were significantly hypertrophic and the basal membrane of the aorta was significantly thick-ened in the control group and such changes were alle-viated in the pAT1a-shRNA1, pAT1a-shRNA2 and valsartan groups. Compared with the control group, pAT1a-shRNA1 and pAT1a-shRNA2 groups had low-ered expression of AT1 receptor (in the myocardium and the thoracic aorta (all P 0.05). We conclude that RNAi targeting AT1a receptor inhibits the development of renovascular hypertension and the accompanying cardiac hypertrophy. RNAi technology may become a new strategy of gene therapy for hyper-tension.