Background and Aims: Engulfment of oxidized low-density lipoprotein (ox-LDL) by macrophages to form foam cells is a key hallmark of the atherosclerotic cardiovascular disease, a leading cause of death in patients with diabetes. Recent application of single cell RNA sequencing (scRNA-seq) of CD45+ cells identified 13 immune cell types with three distinct macrophage populations including Trem2hi foamy macrophages in western diet fed Apoe-/-. Although it is evident that cellular phenotypes are altered by the diabetic environment, the molecular mechanisms underlying diabetes-induced foam cell formation are not known. We applied scRNA-seq to identify cell specific gene expression signature of the diabetic aorta. Further mechanistic experiments were performed in human THP-1-derived macrophages.