Abstract: Chimeras are important materials for the study of mammalian reproduction and development. There has been a long history of using chimeras to tract cell lineage and cell fate transitions during development. Particularly advances related to the identification and generation of various pluripotent stem cells, has enriched the variety of mammalian interspecies chimeras, and provided new ways to understand embryonic development. The knowledge of chimeras accelerated the clinical application of organs generated from chimeras. This review introduces the origin and development of mammalian interspecies chimera research, and describes the role of pluripotent stem cells in driving the study of interspecies chimera research, and looks forward to the trends and issues facing interspecies chimeras.