Aim To investigated the role and mechanism of macrophage in endothelial dysfunction and cardiac hypertrophy in AngⅡ-induced hypertensive mice. Methods C57BL/6 mice were randomly divided into four groups:normal+PBS group, normal+clodronate liposome (CL) group, Ang Ⅱ+PBS group, Ang Ⅱ+CL group. PBS or CL was injected via tail vein,and Ang Ⅱ was delivered by implantation of osmotic mini-pump. The systolic blood pressure (SBP) was measured by tail-cuff method, SBP was measured at 3 time points:at baseline, 7 days and 14 days after AngⅡ infusion. HE staining was used to measure myocardial hypertrophy, endothelium dependent relaxation to acetylcholine in aortic rings was determined by organ chamber bath, the protein expression of p-eNOS, p-ERK1/2 , TNF-α, IL-1β, TGF-β1, fibronectin was determined by Western blot. Results Compared with the normal+PBS mice, AngⅡ+PBS significantly increased systolic blood pressure (44%,P<0.05), macrophage infiltration in myocardial tissue (54%, P<0.05), heart weight (29%, P<0.05) as well as single myocardial cell area (48%, P<0.05), impaired acetylcholine-induced endothelium dependent relaxation (E_max-35%, P<0.05). The treatment with CL significantly reduced SBP (-25.28%, P<0.05), the area of single myocardial cell (-38.83%, P<0.05), and improve acetylcholine-induced endothelium dependent relaxation (E_max 12.63%, P<0.05) in AngⅡ hypertensive mice. CL treatment also restored the expression of p-eNOS, p-ERK1/2, TNF-α, IL-1β, TGF-β1, fibronectin induced by AngⅡ (P<0.05). Conclusions The results demonstrate that CL protects against AngⅡ-induced endothelial dysfunction and myocardial damage and remodeling, the underlying mechanisms may involve reduction in myocardial macrophage infiltration and macrophage-derived cytokines.