RATIONALE AND OBJECTIVES. Magnetic resonance microscopy (MRM) has evolved from a technical curiosity to a tool with which researchers can study important disease models. But MRM is not simply an extension of clinical magnetic resonance imaging. In this article, the unique adaptations of MRM required in the study of carotid artery disease are outlined. The techniques of MRM are integrated into a specific model of carotid artery disease in the rat to allow in vivo studies of vascular wall thickening after removal of the vascular endothelium. METHODS. Imaging was performed at 300 MHz in 250-gm Sprague-Dawley rats using surgically implanted radiofrequency coils to localize the region of interest and to provide an increase in the signal-to-noise ratio over that of volume or surface coils. A three-dimensional Fourier encoding sequence was modified with flow-dephasing gradients to minimize signal and artifacts from moving blood. RESULTS. In vivo images were acquired with spatial resolution of 25 × 25 × 400 ixm and signal-to-noise ratio more than sufficient to define the morphology of the vascular wall. Significant changes in the intensity and distribution of signal were visible in the area surrounding the vessel after angioplasty. CONCLUSIONS. Signal-to-noise improvements from surgically implanted coils coupled to a three-dimensional radiofrequency- refocused sequence with flow-dephasing gradients were sufficient to define the wall of the carotid artery. The diffusionweighted pulse sequence detects signal changes in the area surrounding the vessel after angioplasty. The MRM techniques described and the contrast observed allow us, for the first time,to follow in vivo the early stage of developing atherosclerosis in the vessel wall and closely surrounding tissue.