Aim To assess the effects of vitamin K on calcification and the expression of Toll-like receptor 2 （TLR2） as well as Toll-like receptor 4（TLR4） in aortic artery of ApoE^－/－ mice. Methods Eighteen 6-week-old male ApoE^－/－ mice were randomly divided into model group,interventional group and control group. Model group and interventional group were fed with high-fat diet,while control group were fed with normal diet. Mice in interventional group were administered orally with vitamin K2,once a day for 12 weeks. All mice were sacrificed when the mice were 19 weeks old,blood was collected and plasma triglyceride （TG）,total cholesterol （TC）,high density lipoprotein cholesterol （HDLC）,low density lipoprotein cholesterol （LDLC） were measured. Aortic sections were stained with hematoxylin and eosin （HE） or Von Kossa,and observed under microscope. Calcium content and alkaline phosphatase activity of aorta were measured to determine the degree of vascular calcification. The expressions of TLR2 and TLR4 protein and mRNA levels in aotic sections of mice were detected by immunohistochemisty and qRT-PCR respectively. Results HE staining demonstrated significant thickening of the intima,with typical atherosclerotic plaque formation in model group mice,and von Kossa staining showed spotty black clumps of aortic calcification under the fibrous cap plaque,while intervention group had atherosclerotic plaques without the formation of significant calcium deposits The quantitative analysis showed that aortic vascular wall calcium and alkaline phosphatase activity were significantly lower in the intervention group than that of the model group （P<0.01） Immunohistochemical staining showed that TLR2,TLR4 mainly expressed in atherosclerotic plaques,qRT-PCR confirmed that the expression of TLR2 and TLR4 was significantly higher in the model group mice aorta （P<0.05）,while the expression level of TLR2 and TLR4 mRNA or protein were significantly lower in intervention group aortic than in the model group. The expression level of TLR2 and TLR4 mRNA in mice aorta tissue was positively related to the content of calcium（r0.77 and r0.79,respectively,both P<0.001）. Conclusions Vitamin K2 can reduce calcium content and alkaline phosphatase activity,and inhibit intimal calcification induced by high-fat diet in ApoE^－/－ mice. The results suggest that the effects of vitamin K2 on calcification of aortic artery may be associated with the regulation for the expression of TLR2 and TLR4.