Blood-brain barrier (BBB) prevents effective chemotherapy of brain tumors. Intra-arterial (IA) injection of hyperosmotic mannitol has been attempted for many years to permeabilize the BBB, however due to high variability, this procedure never became a routine clinical practice. We have previously shown that real-time MRI may circumvent that obstacle in large animal model. However, for drug screening purposes the mouse model if preferred. Here, we have shown that real-time, interventional MRI is also instrumental to precisely open BBB in rodents, and more importantly combining it with subsequent delivery of chemotherapeutic drug melphalan provides therapeutic benefit warranting consideration of clinical application.