This study for the first time provides evidence that sitagliptin may inhibit HG-induced alterations including proliferation, migration, apoptosis and calcification in cultured VSMCs, probably through the inhibition of ERK1/2 signaling pathways, revealing the favorable effects of sitagliptin for preventing the occurrence of vascular calcification and atherosclerosis in diabetes. The gene discussed is MAPK3; the disease is atherosclerosis.