Imaging of in vivo model systems, especially mouse models, has revolutionized our understanding of normal and pathological developments. However, mice present several challenges for imaging. They are living and therefore breathing organisms with a fast heart rate (>500 beat/min), which necessitates the need for restraints and positioning controls that do not compromise their normal physiology. We present here a device that immobilizes the rear legs of a mouse while retaining the ability to position both the hind feet and legs for reproducible imaging deep below the skin's surface. The device is highly adjustable to accommodate mice, 5 weeks of age and older. The function of this device is demonstrated by imaging the vasculature ∼250 μm beneath the skin in the hind leg. Whereas the overall dimensions are for a motorized stage (Märzhäuser Wetzlar GmbH, Wetzlar, Germany), minor modifications would allow it to be customized for use with most commercially available stages that accept an insert.