Objective：To investigate the effect of glucagon like peptide-1（GLP-1）on the calcification of aortic valve in mice fed with high fat and cholesterol diet，and to reveal the protective effect and mechanism of GLP-1 in the occurrence and development of calcified aortic valve disease（CAVD）. Methods：Thirty six C57BL/6 mice（8 weeks old，female）were randomly divided into four groups（n=9）. The normal diet group and the GLP-1 control group were given normal diet，and the high fat diet group and the GLP-1 intervention group were fed with high fat and high cholesterol diet + vitamin D2. The GLP-1 control group and the GLP-1 intervention group were additionally treated with GLP-1. After 12 weeks，the two-dimensional echocardiographic data of mice in each group were measured，including aortic valve area（AVA），left ventricular ejection fraction（EF），valve leaf thickness（T），left ventricular end systolic diameter（LVDs），transvalvular velocity（TV）. Then the serum calcium concentrations were measured，and von Kossa staining was used to observe the calcification of valve tissue，and immunohistochemistry to detect the expression of osteopontin（OPN）and p38 protein in the aortic valve samples. Results：① In the normal diet group，the GLP-1 control group and the GLP-1 intervention group，T，TV，LVDs and serum calcium concentration were lower than those in the high fat diet group，while AVA and left ventricular EF were higher than those in the high fat diet group（P < 0.05）. ② The expressions of OPN and phosphorylated p38（p-p38）in the aortic valve samples of the normal diet group，the GLP-1 control group，the GLP-1 intervention group were significantly lower than that of the high fat diet group（P < 0.05）. Conclusion：GLP-1 can inhibit the calcification of aortic valve by inhibiting the expression of p-p38 in mice.