Alterations in platelet function have been observed in a number of diabetic states. Increased responsiveness to platelet-aggregating agents in diabetes associated with increased catecholamine production and/or turnover suggested that heightened sympathetic activity may contribute to this increased platelet aggregation response. To investigate this possibility, we made male Wistar-Furth rats diabetic with streptozotocin and treated them either with adrenergic inhibitors (clonidine, yohimbine, reserpine) or saline. After 2 weeks, arterial blood samples were collected in 3.8% sodium citrate or acid citrate dextrose (ACD). Platelet-rich plasma (PRP) was prepared, and platelet aggregation studies were conducted directly or conducted on washed platelets prepared from PRP collected with ACD. Platelet aggregation in response to ADP by PRP was reduced while the rate of disaggregation was increased in platelets from diabetic animals when compared to controls. However, platelet aggregation in response to ADP in washed platelets was increased in diabetic animals when compared to controls. Clonidine, reserpine and yohimbine significantly decreased the diabetes-induced increase in maximum aggregation. Thrombin-induced aggregation was not altered by diabetes or any of the treatments. The platelet size was increased in the diabetic animals and was decreased toward controls by clonidine, reserpine and yohimbine treatment. These studies suggest that diabetes increases platelet aggregation response in diabetic rats, and that blockage or suppression of adrenergic activity reverses or attenuates the diabetes-induced hypersensitivity to ADP.