Aim To investigate the method and value of anti-intercellular adhesion molecule-1 (ICAM-1) nano targeted ultrasound bubbles in detecting early inflammation of atherosclerosis (As) and ultrasound molecular imaging. Methods Anti-ICAM-1 nano targeted ultrasound bubbles were prepared by biotin-avidin method. 20 experimental rabbits were randomly divided into 4 groups:control group, 2-week modeling group, 4-week modeling group and 6-week modeling group, with 5 rabbits in each group. The control group was not treated with any treatment. The As models were established by surgical balloon injury and high-fat cholesterol diet in 2-week modeling group, 4-week modeling group and 6-week modeling group. Contrast-enhanced ultrasound was performed in each group to obtain the contrast parameters such as peak intensity (PI), time to peak (PPT), area under curve (AUC) in region of interest. At the end of the experiment, pathological examination was performed on the target abdominal aorta. Results Preparation of nano targeted ultrasound bubbles:the binding rate of ICAM-1 antibody to nano ultrasound bubbles was 72.6%. Contrast enhanced ultrasound:in the control group, the contrast agent of vascular cavity and vessel wall basically disappeared at the same time; 2 min after the injection of contrast agent in each modeling group, the contrast agent in the vascular cavity faded, and the local vascular wall was still developed and enhanced. The analysis of targeted contrast-enhanced ultrasound curve at the thickest part of abdominal aorta showed that PPT of the four groups had no significant difference with the extension of modeling time (P＞0.05); PI and AUC of the four groups gradually increased with the extension of modeling time (P＜0.05).HE staining:the vascular wall endothelial cell of the control group were arranged completely; the vascular smooth muscle of the model group proliferated obviously; the lipid plaques were formed in 2-week modeling group and 6-week modeling group, and more significantly in the 6-week modeling group. Immunohistochemical staining:the mean integral optical density (IODM) value of ICAM-1 positive staining in abdominal aorta of four groups increased gradually with the extension of modeling time (P＜0.05). Correlation analysis:the angiographic parameters PI, AUC were positively correlated with the IODM value of ICAM-1 positive staining in abdominal aorta (r＝0.835, P＜0.05; r＝0.868, P＜0.05). Conclusion Anti-ICAM-1 nano targeted ultrasound bubbles can identify the early inflammation of As at the molecular level, and provide more objective and quantifiable contrast-enhanced ultrasound parameters for early detection of As vascular inflammatory lesions.