Objectives : Cellular death by apoptosis is an active process, depending on gene transcription and protein synthesis. It was reported that nitric oxide can induce apoptosis in several cancer cell-lines. We have previously observed that proliferation of Ll210 cells was inhibited by the administration of Gleditsiae Spina water extract (GE). In this present study, the mechanism of inhibitory action on the proliferation of L l210 cells was examined. Methods : The cell proliferation was determined by MTT assay and DNA fragmentation was determined by a flow cytometry. Results : The administration of GE decreased proliferation of L1210 cells and enhanced DNA fragmentation in vivo system. DNA fragmentation of L1210 cells was enhanced by co-culture of peritoneal macrophages obtained from GE-administered mice in vitro and it was partly inhibited by L-NMMA, nitric oxide synthetase inhibitor. In addition, GE increased nitric oxide production from peritoneal macrophages of L1210-transplanted mice. Conclusions : These results suggest that the inhibitory action of GE on proliferation of transplanted-L1210 cells is partly caused by an induction of apoptosis via production of nitric oxide in macrophages.