OBJECTIVE: To study the effect of Bushen Jiangzhi formula(BSJZF) on atherosclerosis(AS) in apolipoprotein E knockout(apo E-/-) mice and the underlying mechanism.METHODS: We used a high fat diet to induce AS in apo E-/-mice. The mice were randomly divided into four groups: model, BSJZF, atorvastatin, and3-methyladenine groups. Syngeneic C57 BL/6 mice of the same age were used for the control group.Autophagosomes in the aorta were examined by transmission electron microscopy. Morphology, lipid accumulation, and collagen deposition in the aorta were examined by hematoxylin and eosin, Oil Red O, and Masson's staining, respectively. Serum levels of tumor necrosis factor alpha(TNF-α), interferon gamma(IFN-γ), and interleukin 10(IL-10)were measured by enzyme-linked immunoassays.Protein expression of microtubule-associated protein light chain 3(LC3), Beclin 1, and p62 in the aorta were examined by Western blot analyses.RESULTS: Apo E-/-mice fed a high fat diet exhibited AS symptoms including less autophagosomes in the aorta, higher serum levels of TNF-α, IFN-γ, and p62, and lower serum levels of IL-10, LC3, and Beclin 1. Treatment with BSJZF significantly reduced the area of the aortic plaque, decreased expression of TNF-α, IFN-γ, and p62, and increased expression of IL-10, LC3, and Beclin 1.CONCLUSION: Our findings suggest that BSJZF promotes autophagy and reduces inflammation by regulating the expression of autophagy-related proteins LC3, Beclin 1, and p62, thereby effectively treating AS.