As a condition of metabolic syndrome, the prevalence of hypertension increased rapidly in the past three decades and consistent hypertension causes various complications,which impair life quality and even be life-threatening. Angiotensinogen, also known as AGT, is the sole precursor of angiotensin peptides in the RAAS pathway, which is the most carefully studied mechanism of blood pressure and volume regulation. RNAi therapies targeting AGT is a promising approach to treat hypertension and related organ damages. Given that the action of RNA interference drugs based on the complementary base pairing, mouse models for preclinical evaluation on AGT target are limited. In this study, we initially generated AGT humanized mice by introducing the entire AGT gene into the Rosa26 site. Despite the presence of a large amount of human AGT in hAGT mice,the inability of rodent RENIN to convert human AGT to AngI prevents the spontaneous development of hypertension. Therefore, we developed a modified human RENIN virus as a flexible tool to induce the persistence hypertension on our novel AGT humanized mice.