CPT-11 is an effective antitumor agent for gastrointestinal malignancy, but the optimum route of administration is unclear. Intraperitoneal administration of this agent was compared with intravenous administration in mouse models of peritoneal seeding and liver metastasis. The peritoneal seeding model and liver metastasis model were established by inoculation of colon 26 tumor cells into the peritoneal cavity and spleen of female BALB/c mice, respectively. CPT-11 (40 mg/kg) was injected intraperitoneally or intravenously on days 2 and 5 after inoculation of tumor cells. Intraperitoneal administration of CPT-11 was significantly more effective than intravenous administration for control of both peritoneal seeding and liver metastasis. Intraperitoneal administration of CPT-11 may be a more efficient form of adjuvant chemotherapy for prevention of both peritoneal seeding and liver metastasis in patients with gastrointestinal cancer.