A micro-PET/CT system was developed by combination of an in-house micro-CT and a microPET R4 scanner. The cone-beam micro-CT consists of a rotational gantry that fits an X-ray tube, a CCD-based X-ray detector, and motor-driven linear stages. The gantry was designed to be coaxial with the scanner of microPET R4. It can be moved for the convenience of mounting the Ge-68 point-source holder for PET’s calibration. The image volumes obtained from two modalities is registered by a pre-determined, inherent spatial transformation function. This hardware-approach fusion, which provides accurate and no labor-intensive alignment, is suitable for mass scanning. The micro-PET/CT system has been operated successfully. Merging the anatomical and functional images benefit studies of the small animal imaging.