Enhancing antitumor activity and minimizing treatment side effects are important issues in cancer therapy. One method to deal with these issues is the utilization of a drug delivery system (DDS). In this study, we developed a novel drug administration pump, a mechanically controlled DDS (M-DDS). The antitumor activity of 5-fluorouracil (5-FU) (15 or 30 mg/kg/day) was evaluated in comparison with systemic intraperitoneal (i.p.) administration for 7 days in a rat model of human pancreatic cancer. The M-DDS was superior to i.p. administration in enhancing antitumor activity and also prolonging median survival from 69 to 85 days at the lower drug dose (15 mg/kg/day). In addition, toxicities in liver, kidney and spleen were found in animals receiving i.p. administration, whereas rats receiving M-DDS treatment did not show these toxicities. The concentration of 5-FU in tumors 1 day after the completion of treatment was considerably higher in rats receiving M-DDS treatment. These results suggest that this novel M-DDS may be a powerful tool for the treatment of pancreatic cancer in combination with conventional chemotherapeutic drugs, offering strong antitumor activity with fewer toxicities. This novel M-DDS, consisting of a control circuit and drug reservoir/pump unit, may be a useful tool for the treatment not only of pancreatic cancer but also of various other accessible cancers for which there is no effective treatment, such as bile-duct and brain tumors.