Aim To investigate whether miR-31-5p could promote progression of atherosclerosis via inhibiting insulin-degrading enzyme （IDE）.Methods To establish the effect of miR-31-5p on the 3’UTR of human IDE, the bioinformatics analysis and dual luciferase assay were performed. To investigate the impact of miR-31-5p on IDE expression and cholesterol homeostasis, cultured THP-1 macrophages and THP-1 macrophage-derived foam cells were transfected with miR-31-5p mimic or inhibitor. ApoE^－/－ mice administered high-fat diet （HFD） were treated by miR-31-5p agomir. The IDE protein levels were measured by Western blot analysis. The plasma lipid levels in ApoE^－/－ mice were measured by ELISA kit. The hepatic lipid deposition and atherosclerotic lesions in ApoE^－/－ mice were measured by oil red O.Results IDE was a potential target of miR-31-5p according to the results of bioinformatics analysis and dual luciferase assay. IDE protein levels were remarkably down-regulated by miR-31-5p in THP-1, hepatic and aortic tissue（P<0.05）. The lipid levels in THP-1 macrophage-derived foam cells and ApoE^－/－ mice plasma were significantly up-regulated by miR-31-5p（P<0.05）. Meanwhile, a significant increase of hepatic lipid deposition and atheromatous plaque formation in ApoE^－/－ mice were induced by miR-31-5p（P<0.05）.Conclusion miR-31-5p promotes progression of atherosclerosis via inhibiting insulin-degrading enzyme.