Abstract: Objective To investigate the relationship between the levels of serum adipokine retinol binding protein 4（RBP4） and essential hypertension, and to explore the role and mechanism of RBP4 in the activation of adipocyte renin-angiotensin system（RAS） and elevation of blood pressure. Methods（1）From December 2016 to March 2019, 96 hypertensive patients without antihypertensive drugs and 64 healthy non-hypertensive physical examiners with normal blood pressure（control group） in the Second Affiliated Hospital of Nanjing Medical University were enrolled. The difference in serum RBP4 levels between the two groups was compared, and the relationship between serum RBP4 and hypertension was analyzed by multivariate logistic regression.（2）In primary mouse white adipocytes, RBP4 was overexpressed by adenovirus transfection, and the protein expression of Toll-like receptor 4（TLR4） and RAS key genes were detected by Western blot. The levels of angiotensinⅡ（AngⅡ） in the supernatant were measured by enzyme-linked immunosorbent assay. The effect of TLR4 inhibitor TAK242 on RBP4 overexpression was also determined. Results Serum RBP4 levels were significantly higher in patients with essential hypertension than in control population 30.1（23.8-40.7） vs 25.1（20.1-31.1） mg/L, Z=-5.381, P＜0.01. Multivariate logistic regression analysis showed that RBP4 was independently associated with hypertension（OR=1.10, 95%CI 1.06-1.14, P＜0.01）. The expression of TLR4, as well as the key RAS genes-angiotensinogen, angiotensin-converting enzyme, renin 1 structural（Ren 1） and angiotensin Ⅱ type 1 receptor, and the levels of AngⅡ in cell supernatant were significantly increased in RBP4-overexpressed adipocytes. Whereas, TAK242 inhibited the upregulation of RAS gene expression and elevation of AngⅡ in supernatant of adipocytes induced by RBP4 overexpression（P＜0.05）. Conclusions Serum RBP4 is associated with hypertension. RBP4 activates the RAS system via TLR4 in adipocytes which may be one of the molecular mechanisms of RBP4 elevating blood pressure.