There is no consensus on whether iodixanol is superior to iohexol. This study aimed to compare the effects of iodixanol and iohexol on circulating endothelial microparticles (EMPs) in stable coronary artery disease (CAD) patients with diabetes mellitus (DM), and also their cytotoxic effects on human umbilical vein endothelial cells (HUVECs) .in vitro100 CAD patients with DM were randomly assigned to receive iso-osmolar contrast medium iodixanol (group I) or low-osmolar iohexol (group II) during coronary angioplasty. An additional 49 CAD patients without DM receiving iohexol were recruited as group III. Circulating CD31/CD41a EMPs, CD62E EMPs, and CD31/CD41a platelet microparticles (PMPs) were determined by flow cytometry. , the cytotoxic effects of iodixanol and iohexol on HUVECs were determined.+Circulating CD31/CD41a EMPs and PMPs were significantly increased after angioplasty in all 3 groups, while CD62E EMPs significantly decreased in group I. CD31/CD41a EMPs and PMPs were significantly higher in group II than group I or III. , both contrast media induced EMP release and inhibited the viability and induced apoptosis of HUVECs, as well as increasing Bax and cleaved caspase-3 and decreasing Bcl-2. The above effects were less evident in iodixanol than in iohexol.+Compared with iohexol, iodixanol induces less release of EMPs in both CAD patients with DM during angioplasty and HUVEC culture, which is associated with less pronounced proapoptotic effects of iodixanol on HUVECs.in vitroThis study is registered with ChiCTR-TRC-14005183.