Contrast-induced acute kidney injury (CIAKI) is the most-common form of in-hospital drug-induced acute kidney injury and occurs in 1 to over 50% of patients undergoing intravascular contrast media (CM) administration. Numerous risk factors for CIAKI have been described, the most prominent among them is pre-existing kidney disease such as diabetic nephropathy. The pathogenesis of CIAKI appears to be caused, at least in part, by renal vasoconstriction and renal ischemia leading to the generation of reactive oxygen species (ROS). Diabetes is associated with increased sensitivity to renal vasoconstrictors including CM agents and is also associated with dysfunctional renal handling of ROS, making diabetics particularly susceptible to CIAKI. At present, there are limited srtategies for the prevention of CIAKI among them the administration of the antioxidant N-acetylcysteine (NAC) and intravenous hydration. In light of the rising prevalence of diabetes worldwide and the high risk it represents for the development of CIAKI and CIAKI-associated cardiovascular mortality, a lucid understanding of the pathogenesis of CIAKI and diabetic nephropathy is indispensable. The current review addresses the role of ROS in the pathogenesis of CIAKI in the diabetic renal milieu and discusses current and potential novel treatment modalities for the prevention of CIAKI in diabetic patients.