Aim To investigate the effect of total flavone of radix puerariae on atherosclerotic plaque formation of aortic sinus in apolipoprotein E gene deficient(ApoE~(-/-)) mice. Methods 32 ApoE~(-/-) mice were divided randomly into four groups: model group,total flavone of radix puerariae low-dosage group(15 mg/kg everyday),total flavone of radix puerariae high-dosage group(85 mg/kg everyday) and atorvastatin calcium positive control group(5 mg/kg everyday).There were 8 mice in each group.The treatment group was stomach perfusion with relevant drug,the model group was stomach perfusion with equal amount of normal saline,and both group were medicated for 12 weeks and were fed with general diet.The routine biochemical method was used to measure total cholesterol,triglyceride and high-density lipoprotein-cholesterol in serum;and the serial paraffin section and Hematoxylin and eosin(HE) staining of aortic root were used to observe the histomorphological change of aortic sinus and measure the size of aortic sinus plaque in ApoE~(-/-) mice. Results A total of 65 plaques were detected in four groups.Despite the typical middle/advanced pathological changes of aortic sinus(such as fibrous plaque and/or atheromatous plaque),four groups were different in histological observation.In model group,some plaques were bigger,merged into flake,aortic wall thickened diffusively,aortic cavity was narrower.In otal flavone of radix puerariae treatment group and atorvastatin calcium positive control group,the aortic sinus had a more limited plaque lesion and a slighter narrowing of aortic cavity. The ratio of plaque area to aortic cavity area was significantly smaller in total flavone of radix puerariae high-dosage group,total flavone of radix puerariae low-dosage group and atorvastatin calcium positive control group than that in model group,and was significantly smaller in total flavone of radix puerariae high-dosage group than that in total flavone of radix puerariae low-dosage group(p<0.01). Conclusions Total flavone of radix puerariae can inhibit to some extent the progress of atherosclerotic plaque in ApoE~(-/-) mice,which might not be significantly related to its effect of decreasing mice blood lipid.