Aim Atherosclerosis is a chronic inflammatory disease, but the regression of plaques suggests the possibility of reversal of atherosclerotic disease. Thus, the establishment of a model of atherosclerosis regression in mice is of great significance for elucidating the mechanism of plaque regression. Methods In ApoE－/－ mice, three types of carotid ligation were performed to induce different types of blood flow. To establish the regression model, partial carotid ligation with a slipknot was firstly used to induce disturbed flow. After feeding on a high-fat diet for 2 weeks, the slipknot was removed, and followed by a chow diet for two weeks. The ultrasonic testing was performed to monitor the blood flow in real time caused afterligation or plaque formation; Sudan Ⅳ staining was used to assess atherosclerotic lesions; immunofluorescence staining with anti MOMA2 was applied to examine monocyte-macrophage infiltration. Results Three types of ligation induced different types of blood flow. The disturbed flow induced the largest atherosclerotic plaque area in ApoE－/－ mice. After restore of blood flow combined with chow diet, atherosclerotic plaques can be significantly reduced and reversed, and the macrophage infiltration also significantly decreased. Conclusion A novel atherosclerosis regression model in mice based on carotid ligation surgery was successfully constructed, which will help to understand the underlying mechanism of atherosclerosis regression.