Objective To explain the protection effect and mechanism of gene transfection of angiotensin converting enzyme 2 (ACE2) towards endothelial cells by observing the effects of gene transfection of ACE2 on vascular endothelial cells of model rabbits with atherosclerosis. Methods The atherosclerosis model of rabbit was established by balloon injuries of endothelial cells and atherogenic diet. Sixteen New Zealand rabbits were randomly divided into the Ad-ACE2 group (transfected by the recombinant adenovirus carrying the ACE2 gene) and Ad-EGFP group (transfected by the recombinant adenovirus without carrying the ACE2 gene). Each group consisted of 8 rabbits. The rabbits of two groups received abdominal aortic injections of ACE2 recombinant adenovirus (2.5×10⁹ pfu/mL) and Ad-EGFP, respectively. After one month, all rabbits were sacrificed and specimens of plaques from abdominal aorta segments were prepared. The protein expressions of ACE2 in atherosclerotic plaques were detected by the Western blotting. The expressions of intercellular adhesion molecule-1 (ICAM-1) and P-selectin protein were evaluated by the immunohistochemical staining. The semi-quantitative analysis was carried out by the oil red O staining. Results The results showed that the expressions of ACE2 protein of the Ad-ACE2 group were significantly higher than that of the Ad-EGFP group (P<0.05). The positive expression rates of ICAM-1 and P-selectin protein in plaques of the Ad-ACE2 group were significantly lower than those of the Ad-EGFP group [(16.95±3.09)% vs (24.81±4.78)% and (16.22±2.45)% vs (23.46±3.28)%, respectively]. The differences between two groups were statistically significant (P<0.01). The lipid contents in plaques of the Ad-ACE2 group (41.77±3.17)% were significantly lower than those of the Ad-EGFP group (59.55±1.53)%. The differences between two groups were statistically significant (P<0.05). Conclusion ACE2 gene transfection can protect the endothelial cells of rabbits and inhibit the development of atherosclerosis by down-regulating the expressions of ICAM-1 and P-selectin protein.