Background: Ang II plays important roles in controlling stability of BP. ERAP1 can regulate BP by reducing the level of Ang II. However, the downstream mechanisms of activated Ang II which are activated by ERAP1 deletion have not been identified. Methods: Tail-cuff was used to measure BP in the ERAP1 deficient and wt mice. Ang II were evaluated by LC-MS. Aldo were measured with ELISA kits. PAH clearance was collected and used to calculate renal plasma flow (RPF) . RT-qPCR, immunochemistry staining, and bulk RNA sequencing were applied to identify the mechanisms. Two medications (Enalapril and Amlodipine) were used as control. BP data was collected to examine the influence of ERAP1 rs30187 risk allele carriers to SSBP. Results: Ang II were upregulated and induced hypertension in ERAP1 deficient mice. BP did not show sex differences, while Ang II expression exhibited sex dimorphism. Along with an increase of Aldo levels, the expressions of ERAP1 and CYP11B2 were co-knockdown in ZG cells in male ERAP1+/- mice. Different activated genes were further detected. While in ERAP1+/- females, decreased RPF and lower ERAP1 and CD31 expressions in endothelial cells were observed. Enalapril took effects in dropping BP and decreasing Aldo production. Smaller BP decline and no difference of RPF in females was confirmed in Amlodipine group. People <51 years old with the ERAP1 rs30187 risk allele exhibited increased SSBP. Conclusions: ERAP1 exerted BP control by regulating Ang II. In male ERAP1+/- mice, the primary regulated mechanism occurred in adrenals, where overexpressed Ang II targeted ZG cells, activated Aldo production pathway. In female ERAP1+/- mice, the prominent mechanism was dependent on the alterations of vascular, elevated Ang II downregulated endothelial cells' proliferation, decreased RPF and exacerbated renal vascular function. Enalapril had stronger effects in regulating RAAS and Amlodipine played important roles in relaxing the vessels.