Objective To investigate the antihypertensive effect of SPH3127 and its mechanism of vascu⁃ lar endothelial protection. Methods Eighty male SD rats were randomly divided into a sham operation group， model group，high ⁃dose SPH3127 group（20 mg/kg），and low ⁃dose SPH3127 group（10 mg/kg）. Systolic blood pressure（SBP），interleukin⁃6（IL⁃6），tumor necrosis factor⁃α（TNF⁃α），endothelial nitric oxide synthase（eNOS）， and inflammatory injury were measured. Human umbilical vein endothelial cells（HUVECs）were divided into a control group，AngⅡ（1 μmol//mL）group，and SPH3127（10 nmol//mL）group. The ability of proliferation and migration，and mRNA expression levels of eNOS and FXYD1 were detected. Results SPH3127 treatment signifi⁃ cantly reduced blood pressure，increased intimal integrity，decreased expressions of IL⁃6 and TNF⁃α，and increased eNOS，especially in the high⁃dose group（P < 0.05）；The ability of proliferation and migration in HUVECs were increased，and the mRNA expression levels of FXYD1 and eNOS were increased （P < 0.05）. Conclusions SPH3127 can reduce blood pressure in rats. By inhibiting inflammation and promoting the expression of FXYD1，it plays a certain role in protection of vascular endothelium.