This study aimed to explore the effect of Bif idobacterium animalis F1-7 on the improvement of atherosclerotic inflammation. Arteriosclerosis model ApoE^-/- mice were orally administered with B. animalis F1-7 for 12 weeks. The probiotic intervention reduced the plaque areas in aorta and the accumulation of macrophages, and downregulated the expression of toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB) pathway to reduce the levels of inf lammatory factors. The widely-targeted metabolomics analysis showed that acetyl-L-carnitine (ALC) in the intestine of atherosclerotic mice was signif icantly increased after B. animalis F1-7 intervention. Correlation analysis proved that ALC was associated with atherosclerotic inf lammatory response. By using oxidized low density lipoprotein induced macrophage foam cells, we further verif ied that ALC could reduce lipid accumulation and inf lammatory response in foam cells by downregulating the TLR4/NF-κB pathway. Finally, our results revealed that B. animalis F1-7 upregulated the metabolite ALC to downregulate the inf lammatory responses, leading to the reduction of plaque accumulation of atherosclerosis.