Despite advances in therapy, individuals with diabetes remain at high risk of cardiovascular disease and their clinical prognosis following vascular ischemia is worse than that of individuals with normal glucose metabolism. Current evidence suggests that the enhanced thrombotic environment in diabetes represents a key abnormality contributing to the adverse clinical outcome following vascular occlusion in this population. Thrombus formation occurs following a complex process that encompasses both the cellular (represented by platelets) and fluid phase of coagulation, involving a large number of plasma proteins. In the current review, we discuss some of the abnormalities encountered in coagulation factor levels or activity in diabetes. In particular, we focus on the pathological processes that lead to the formation of compact fibrin networks with increased resistance to lysis. We describe current knowledge on the mechanistic pathways responsible for the increased fibrin‑related thrombosis risk in diabetes and explore alternative therapeutic targets. We also briefly cover various management strategies that may help control the enhanced thrombotic milieu in this population of patients at high cardiovascular risk.