A system and method for treating atherosclerotic plaque. The system includes a first catheter including an expandable balloon and a second catheter including a lumen in fluid communication with a distal hole. The method includes inserting the first catheter into a body lumen adjacent to a plaque formation, and deploying a balloon from the first catheter adjacent to the plaque formation. In addition, the method includes inserting the second catheter adjacent to the first catheter, and routing the distal end portion of second catheter along at least a portion of the deployed balloon of the first catheter. Further, the method includes routing at least a portion of the second catheter into a subintimal space adjacent to the atherosclerotic plaque. Furthermore, the method includes injecting a therapeutic agent into the subintimal space adjacent to the atherosclerotic plaque.