Herein, we examined the effect of liraglutide on aortic valve stenosis using a high-cholesterol-diet-induced experimental CAVD model in apolipoprotein E-deficient (Apoe−/−) mice and found that liraglutide blocks aortic valve stenosis through attenuating aortic valve inflammation, VIC osteogenic differentiation, and calcification. This evidence concerns the gene APOE and stricture.