Objective To study the rapid modeling of Western dietary feed and its impact on biological indicators and histopathology in APOE-/- mice.Methods Using 48 female、48 male APOE-/- mice, 48 female、48 male C57BL/6J mice was tested and divided into 8 groups, namely the APOE-/- ordinary breeding feed group (24 female and 24 male each）、 APOE-/- Western Dietary Feed Group (24 female and 24 male each）、 C57BL/6J ordinary breeding feed group (24 female and 24 male each）、C57BL/6J Western Dietary Feed Group. Feed from 3w until the end of the experiment at 20w. After the experiment, serum was collected for biochemical indicators, and the aorta was separated for gross oil red staining and analysis. The root of the aorta was paraffin sectioned and HE stained. Results Western diet did not significantly increase APOE- / -body weight, western diet could significantly improve the blood lipid index of APOE- / -mice, total cholesterol, low density lipoprotein, high density lipoprotein, promote the formation of atherosclerotic plaque, male mice are suitable for the modeling of gross aortic plaque, and female mice are suitable for plaque modeling of aortic arch root. Conclusion Western dietary diet can promote APOE- / -mice, increase the aortic plaque area ratio, shorten modeling time, and improve modeling uniformity.