Objective: To analyze the ultrasonic characteristics of aortic atherosclerosis of Apolipoprotein-E knockout (ApoE-/-) mice in the early stage with ultrasound biomicroscopy (UBM). Methods: Two different age groups of male ApoE-/- mice (8 and 16 weeks, each n=8) were used as experimental groups. Another two groups of age-matched male C57BL/6 mice (8 and 16 weeks, each n=8) were used as control groups. The morphosis of the aortic root, ascending aorta and aortic arch were observed with UBM, and the intima-media thickness (IMT) was measured at aortic root short axis view and compared with corresponding histological measurements in the same vascular section. Results: UBM showed IMT was thicker in ApoE-/- mice than that of the controls at the same age (P<0.01). Blinded UBM-based and histological measurements of IMT showed significant age-dependant increase of IMT from 8 to 16 weeks in Apoe-/- mice (P<0.01). IMT measured with UBM was positively correlated with histological measurement at the same vascular region (r=0.81, P<0.0001). Conclusion: Compared with histopathology, UBM can detect atherosclerotic progression in ApoE-/- mice through measuring IMT of the aorta, especially at the early stage of atherosclerosis.