The current 3D XCAT phantom allows users to manually define the regional myocardial perfusion defect (MPD) as a simple pie-shaped wedge region with reduced activity level in the myocardium of left ventricle. To more accurately and realistically model the MPD, we have developed a new regional MPD model for the 3D XCAT phantom for myocardial perfusion SPECT (MP-SPECT) studies based on the location and the severity of the stenosis in a computer generated coronary arterial tree. First, we generated a detailed coronary arterial tree by extending the large proximal branches segmented from patient CT images to cover the whole heart using an iterative rule-based algorithm. Second, we determined the affected downstream vascular segments of a given stenosis. Third, we computed the activity of each myocardial region as a function of the inverse-distance-weighted average of the flow of the neighboring vascular segments. Fourth, we generated a series of bull's-eye maps of MP-SPECT images of different coronary artery stenosis scenarios. Fifth, we had expert physician readers to qualitatively assess the bull's-eye maps based on their similarity to typical clinical cases in terms of the shape, the extent, and the severity of the MPDs. Their input was used to iteratively revise the coronary artery tree model so that the MPDs were closely matched to those found in bull's-eye maps from patient studies. Finally, from our simulated MP-SPECT images, we observed that (1) the locations of the MPDs caused by stenoses at different main arteries were different largely according to their vascular territories, (2) a stenosis at a proximal branch produced a larger MPD than the one at a distal branch, and (3) a more severe stenosis produced a larger MPD than the less severe one. These observations were consistent to those found in clinical cases. Therefore, this new regional MPD model has enhanced the generation of realistic pathological MP-SPECT images using the XCAT phantom. When combining with the mechanical model of the myocardium, the new model can be extended for the simulation of 4D gated MP-SPECT simulation of a pathological heart with both perfusion and motion defects.