After we prepared exo-polymers (EPS) from Cordyceps sinensis by submerged culture, prophylactic intravenous administration (i.v.) of EPS significantly inhibited metastasis in experimental lung metastasis of colon 26-M3.1 carcinoma. Cytotoxicity against Yac-1 tumor cells of natural killer (NK) cell, which was prepared by i.v. of EPS (100 mug/mouse), significantly augmented 2 days after EPS treatment. When NK cells were depleted by rabbit anti-asialo GM1 serum, even the EPS group totally abolished the inhibitory effect on lung metastasis of colon 26-M3.1 cells. EPS can stimulate innate immune system to inhibit tumor metastasis, and its anti-tumor metastasis is associated with macrophage and NK cell activation.