Tetramethylpyrazine (TMPZ) is an active component that can be extracted from certain plants. In China, this herbal extract is used to treat ischemic vascular diseases. We have assessed the antithrombotic activity of TMPZ using arterial and venous thrombosis models in rats. Antithrombotic activity of TMPZ is at least partly due to its potent antiplatelet effect. We have shown that TMPZ inhibits platelet aggregation induced by ADP, collagen, thrombin, and A23187 but not by diacylglycerol (DAG). Platelets that were induced to produce maximal aggregation could be dispersed by the addition of TMPZ. Platelets could then be reaggregated by the addition of DAG. Studies monitoring intracellular ionized calcium suggest that TMPZ inhibits calcium mobilization from both the extracellular medium and from intracellular stores.