Intraarterial chemotherapy (IAC) is considered effective for the treatment of solid tumors with high local doses of systemically toxic chemotherapeutics. Osteosarcoma, which is often located in the extremities, is a potential target for IAC. However, the efficacy of this treatment modality has varied, and standardized protocols are difficult to establish due to tumor heterogeneity and the limited numbers of patients available for clinical trials. Reproducible experimental models are needed to further investigate IAC in osteosarcoma. Here, we describe a new microsurgical technique for repeated infusion of drugs into the mouse femoral artery for local treatment of experimental intratibial metastasizing osteosarcoma. We successfully achieved 5 catheterizations at 3-d intervals in 70% of the mice tested. Laser speckle imaging indicated a maximal 50% reduction in blood flow around the ankle region of catheterized legs infused with 0.5 mg/kg cisplatin. However, blood flow in the front feet was affected only minimally. Histologic examination of catheterized arteries of saline control or cisplatin-treated mice showed circular fibrinoid media necrosis and partial thrombosis, but total occlusion of the arteries was not observed. The method we describe for repeated transient catheterization of the mouse femoral artery likely will be useful in future studies comparing the efficacies of intraarterial and systemic cisplatin treatment of intratibial metastasizing osteosarcoma in mice under standardized conditions.