Objective：To observe the therapeutic effect of 153Smclodronate on nude mice orthotopically transplanted with human osteosarcoma. Methods: Severe combined immune deficiency (SCID) mice were subcutaneously inoculated with human osteosarcoma cell line HOS8603. The formed tumors were then transplanted into BALB/c nude mice at the tibia for passage; the tumors were harvested for establishing orthotopical mice model of human osteosarcoma. Mice treated with 153SmEDTMP and clodronate group served as controls. The distribution of 153Smclodronate was determined 24 h later. The appearance, tumor weights, Xray examination, histological observation, and survival of mice were compared between the 3 groups. Results: It showed that the distribution of 153Smclodronate in the lesion bone was much higher than that in other organs, with the radioactive ratio of lesion bone to blood being 4 627.11, lesion bone to normal bone being 10.81, and normal bone to liver being 8.41. 153Smclodronate treated mice had a slighter osteolytic reaction and a longer survival period, but the tumor mass was not significantly different compared with those of the control group. Conclusion: 153Smclodronate gathers at the lesion bone and it has good therapeutic effect on the mice model of human oseosarcoma, making it a promising agent for treatment of bone tumor.