Microparticles (MPs) are small vesicles released from cell membrane following cell activation and apoptosis. Elevated levels of circulating MPs have been reported in many cardiovascular diseases and have been proposed as clinical markers for cardiovascular risk. Released MPs carry a range of antigens depending on the type and activation state of their parental cells. Therefore, it has been suggested that MPs may play important roles in the processes of inflammation and the progression of many cardiovascular diseases. Diabetes is commonly associated with microvascular dysfunction. Our recent study found that microvessels of streptozotocin-induced diabetic rats had increased basal permeability and markedly enhanced permeability responses to inflammatory mediators. We also found that diabetic rats had a significantly increased number of circulating MPs. We hypothesized that the elevated circulating MPs in diabetic rats serve as vectors to actively disseminate inflammation to the vascular system. We used flow cytometry to quantify the numbers of MPs and their cell origins. MPs in diabetic plasma was 5.7 ± 0.9 times of that in normal rat, with 80% of these increased MPs exhibiting exposed phosphatidylserine (PS) on their surface (n=9 per group). The functional roles of MPs were examined by perfusing a matched number of MPs isolated from normal and diabetic rat plasma into individually perfused rat mesenteric venules. Each vessel was perfused with isolated MPs for 30 min followed by 10 min of resumed blood flow. When the same vessel was recannulated with BSA-Ringer perfusate, a large number of adherent leukocytes were found in the diabetic MP-perfused vessels. The adhered leukocytes were 17 ± 2.9 and 5.7 ± 0.5 per 100 µm of vessel length in vessels perfused with diabetic and normal MPs, respectively. An increase in hydraulic conductivity (7.1 ± 1.2-fold) occurred when chemoattractant fMLP (10 µM) was applied to vessels with adherent diabetic MPs. Confocal imaging showed that diabetic MPs, not normal MPs, directly adhered on microvessel walls through single vessel perfusion. Blocking PS on the surface of MPs through precoating of Annexin V prevented the adhesion of diabetic MPs to microvessel walls and also abolished MP-mediated leukocyte adhesion. Flow cytometry analysis showed that diabetic MPs had a 6.4 ± 1.1-fold higher PS exposure per MP compared to those in normal plasma MPs. These results suggest that the increased number of MPs, as well as the larger PS surface area of each diabetic MP play an essential role in their interaction with endothelium and subsequent leukocyte adhesion. These results support our hypothesis that increased MPs in diabetic rats are more than simply biomarkers of the disease, but are direct mediators of leukocyte adhesion and actively disseminate inflammation to remote regions of the vasculature.