Tetramethylpyrazine (TMPZ) is an active ingredient of a Chinese herbal medicine. We have previously shown that TMPZ possesses antithrombotic activity in rat thrombotic models. Inhibition of platelet aggregation and promotion of disaggregation contributed to the antithrombotic activity of TMPZ. In this study, we evaluated the antiplatelet actions of TMPZ using human platelets and found that antiplatelet activity of TMPZ included the inhibition of intracellular Ca++ mobilization (mainly the release from internal stores), the enhancement of intracellular cAMP by inhibition of phosphodiesterase activity, and the reduction of GP IIb/IIIa exposure on the surface of activated platelets.