Objective: Recent studies have shown that insulin therapy increased the risk of major cardiovascular adverse events, and the changes of platelet reactivity may be responsible for the clinical outcomes. We attempted to explore the effect of exogenous insulin on platelet function in patients with type 2 diabetes mellitus who were suffering from acute vascular events. Methods: We collected data of 540 diabetes patients with acute ischemic vascular events from the hospital information system. Their platelet reactivity has been reported by the maximum amplitude of adenosine diphosphate-induced platelet-fibrin clots (MAADP) of thromboelastography. The effect of antidiabetic drugs on platelet reactivity was analyzed retrospectively. Stratified regression analysis was carried out to gradually adjust for the demographic data, genetic factors, lifestyle, biochemical indicators, antiplatelet regimen, etc. Results: Univariate linear regression analysis showed that sex, age, body mass index, smoking, low-density lipoprotein, platelet count, CYP2C19*2, antiplatelet regimens, and insulin were related to MAADP. After multiple factors were adjusted, the effect of insulin therapy (95% CI: 0.022-0.664; p =0.036) on MAADP was always statistically significant. Conclusions: Exogenous insulin effects significantly on the level of MAADP in diabetic patients with acute ischemic vascular events, which may be not conducive to antiplatelet therapy.