To investigate the effect of “middle-regulating and vessels-dredging” acupuncture method on hepatic microRNA-223(miR-223)，flavin-containing monooxygenase 3(FMO3)，and plasma trimethylamine-N-oxide(TMAO) levels in a mouse model of atherosclerosis(AS)，and to explore its potential mechanism in AS treatment.Methods:Eleven C57BL/6J mice served as the blank group，and 31 apolipoprotein E-knockout(ApoE-/-) mice，serving as the modeling group，were fed a high-fat diet for 8 weeks to induce AS.Successfully modeled mice were randomly assigned to a model group，a Western medicine group，and an electroacupuncture group(n=10 for each group) according to random number table.The blank and model groups received no intervention.The Western medicine group was administered atorvastatin calcium diluent at 1.517 mg/(kg·day) via gavage，while the electroacupuncture group received treatment at Neiguan(PC 6)，Tianshu(ST 25)，and Zusanli(ST 36) for 11 weeks.Body weight changes were recorded during the intervention.After treatment，hematoxylin-eosin(HE) staining was used to assess aortic pathology.Serum lipid profiles were measured using a microplate method.FMO3 protein expression in the liver was analyzed via Western blot.Hepatic miR-223 and FMO3 mRNA levels were measured by qRT-PCR.Plasma TMAO levels were quantified by ELISA.Results:Compared with the blank group，the model group exhibited atherosclerotic changes in the aorta，increased body weight，dyslipidemia，decreased miR-223 expression，elevated FMO3 expression，and increased plasma TMAO levels(P<0.01 or P<0.05).Compared with the model group，both the Western medicine and electroacupuncture groups showed milder aortic lesions，reduced body weight，improved lipid profiles，increased miR-223 expression，decreased FMO3 expression，and lower TMAO levels(P<0.01 or P<0.05).Conclusion:The “middle-regulating and vessels-dredging” acupuncture approach may ameliorate AS by upregulating miR-223 and inhibiting the FMO3/TMAO pathway，thereby modulating lipid metabolism