In vivo small animal imaging provides a powerful tool for the study of a variety of diseases. Magnetic resonance imaging (MRI) has become an established technology for the assessment of therapies. In this study, we used high-resolution MRI to evaluate polycystic kidney disease (PKD) in transgenic mice. We used a customized mouse coil to acquire serial MR images from both wide-type and transgenic PKD mice immediately prior to, and 2-week and 4-week after therapy. We developed image segmentation, registration and visualization methods for this novel imaging application. We measured the kidney volumes for each mouse to assess the efficacy of the therapy. The segmentation results show that the kidney volumes are consistent, which are 348.7 ± 19.7 mm3 for wild-type mice and 756.3 ± 44.1 mm3 for transgenic mice, respectively. The image analysis methods provide a useful tool for this new application.