We examined the mechanism of the reduction of metastatic liver tumors in rats treated with angiogenesis inhibitor TNP-470 on the histological basis of patterns of tumor cell death. Metastatic tumors were developed by intravenous injection of AH-130 cell line, followed by a dose of TNP-470. Alteration in the size and number of metastatic liver tumors and its cell death pattern were analyzed. The number and size of the metastatic tumors at 2 weeks in untreated rats were larger than those in treated rats. The number of tumors in untreated rats decreased, whereas their size increased. All rats treated were alive and free from tumors after 4 weeks, although all untreated rats died of metastatic tumors. Necrosis was predominant in the tumors of untreated rats, while most tumors in treated rats showed apoptosis. Consequently, the metastatic tumor in untreated rats might grow faster than its angiogenesis, suggesting the occurrence of central necrosis due to apparent ischemia. On the other hand, the tumor in treated rats might be reduce a by weak ischemic stimulus, which triggers apoptosis.