We have previously examined the antiproliferative activity of caffeic acid phenethyl ester (CAPE) and its 20 analogues against six tumor cell lines, and found that CAPE analogues possess selective antiproliferative activity toward the murine colon 26-L5 carcinoma cell line. To extend our study, the effects of CAPE analogues on the metastatic development of murine colon 26-L5 carcinoma cells in the lung were examined. The oral administration of CAPE (5 mg/mice/d) for 7 d after tumor inoculation decreased the tumor weight and the number of tumor nodules in the lung by 50% and 50%, respectively, compared to the control, while CAPE (5 mg/mice/d) administered for 7 d before tumor inoculation showed no significant effect. Besides CAPE, 4-phenylbutyl caffeate, 8-phenyl-7-octenyl caffeate, 2-cyclohexylethyl caffeate and n-octyl caffeate at an oral dose of 2 mg/mice/d caused a 55%, 43%, 55% and 35% reduction of the tumor nodules in their lung metastasis formation, respectively. These results further elaborate the possibility of CAPE and its analogues to become a new class of chemopreventive agents for the treatment of colon cancer metastasis.