As a type of 3D model, the technology of microencapsulation holds significant promise for tissue engineering and cell therapy due to its unique performance. The microenvironmental factors within microcapsules play an important role in influencing the behaviors of encapsulated cells. The aim of this review article is to give an overview on the construction of the microenvironmental factors, which include 3D space, physicochemical properties of alginate matrix, cell spheroids, nutritional status, and so on. Furthermore, we clarified the effect of microenvironmental factors on the behaviors of encapsulated cells and the methods about improving the microenvironment of microcapsules. This review will help to understand the interaction of the microenvironment and the encapsulated cells and lay a solid foundation for microcapsule-based cell therapy and tissue engineering. (C) 2012, The Society for Biotechnology. Japan. All rights reserved.