Abstract: OBJECTIVE To explore the effect of 3,4-dihydroxyacetophenone(DHAP) on the expression of Toll-like receptor 4(TLR4) mRNA and protein in activated mouse vascular smooth muscle cells (VSMC), endothelial cells (EC) and macrophage (MC) to observe the change of aortic atherosclerosis at apolipoprotein E knockout (ApoE-/-) mouse treated with DHAP. METHODS Normal thoracic aortas were obtained from 4 adult mice, and the VSMC, EC were cultured. The MC (RAW264.7 cell lines) was obtained from ATCC. The cells were divided into four groups: control group; LPS group; DHAP group; simvastatin group. Changes of TLR4 mRNA and protein were analyzed by RT-PCR and Western blot. In addition, 30 same age male mice of ApoE(-/-) were fed with a Western diet (21% fat, 0.15% cholesterol) for 12 weeks, and these mice were divided into three groups at random including: model group; DHAP treated group receiving DHAP administered via gastric tube at 10 mg·kg^-1·d^-1 for consecutive 12 weeks; simvastatin treated group receiving simvastatin administered via gastric tube at 10 mg·kg^-1·d^-1 for consecutive 12 weeks. The changes of aortic atherosclerosis were analyzed. RESULTS The VSMC, EC and MC pretreated by 1×10^-7 mol·L^-1 DHAP expressed TLR4 mRNA and protein lower than unpretreated ones (P<0.01) in activated. The lesions of aortic atherosclerosis were inhibited in two treated groups. CONCLUSION It suggested that DHAP could be effective for the prevention and treatment of AS, and TLR4 path might be the mechanism of DHAP to treat AS.