Platelet aggregation induced by cancer cells is an indispensable step for hematogenic metastasis. In these studies, we investigated whether platelet aggregation accelerates hematogenic metastasis of cancer cells in mice and the effect of cordycepin (3'-deoxyadenosine), a component of Cordyceps sinensis, on hematogenic metastasis accelerated by adenosine-5'-diphosphate (ADP). ADP significantly increased the number of metastatic lung nodules in mice injected intravenously with B16-F1 mouse melanoma cells (B16-F1 cells) in a dose-dependent manner and cordycepin significantly reduced the number of metastatic nodules of B16-F1 cells formed in the lung accelerated by ADP injected simultaneously with B16-F1 cells. These results suggest that ADP accelerated hematogenic metastasis and cordycepin has an inhibitory effect on hematogenic metastasis of B16-F1 melanoma cells via blocking of ADP-induced platelet aggregation in vivo.