Hyperglycemia has been linked to adverse outcomes after myocardial infarction. We characterized the effect of selected concentrations of glucose or mannitol on platelet function in whole blood samples from healthy volunteers and from patients with and without diabetes mellitus. Activation of platelet glycoprotein IIb/IIIa and P-selectin expression was increased similarly after addition of isosmotic concentrations of glucose and mannitol, suggesting that increased osmolarity associated with hyperglycemia increases platelet reactivity.