Intracranial Atherosclerotic Disease (ICAD) is the most common cause of ischemic stroke worldwide. However, incomplete understanding of its pathophysiology and natural history limits the effectiveness of current therapies. These limitations result from the difficulty of obtaining tissue samples of the disease. To work around this obstacle, we developed and validated a rabbit model of intracranial atherosclerosis to better characterize the full course of ICAD. Current studies are evaluating gene-expression traits associated with various stages of the disease, its appearance on vessel wall MRI, and features unique to lesions causing strokes. This research will inform current ICAD management strategies and identify targets for next generation therapies.