The rat represents an excellent mammalian model for broadening medical knowledge, and a wealth of information on its physiology has been obtained from its use as an experimental organism. Furthermore, its ample body size allows various surgical manipulations that cannot be performed on a mouse. Many rat models mimic human diseases and have therefore been used in a variety of biomedical studies, including physiology, pharmacology, and transplantation. In an effort to create specifically designed rats for new biomedical research and the field of regenerative medicine, we develop an engineered rat system on the basis of transgenic technology and succeed in establishing unique rats that possess genetically encoded color probes: green fluorescent protein (GFP), DsRed2 (red liver), Cre/LoxP (red to green), and LacZ (blue and luminescence). In this work, we highlight their characteristics and describe recent applications for tissue engineering and regeneration. Coupled with recent progress in modern imaging systems, these transgenic rats are providing powerful tools for the elucidation of many cellular processes in biomedical science, and may lead to innovative medical treatments.