Some intrinsic ESC-specific markers, cytokines and extracelluar matrix in the microenvironment compose of a complex network to co-regulate ESC self-renewal. The molecular mechanism of signal network maintaining ESC self-renewal was investigated by studying the ESC-specific markers, such as Oct-4 and Nonog recently. Moreover, ESC signal pathways, just like LIF-STAT3, Wnt-β-catenin and BMP-Id ,were further deeply studied. In conclusion, the most important key to maintain ESC self-renewal is the balance among the content of various cytokines, extracelluar matrix, and expressing quantity of intrinsic ESC-specific markers by different signal stimulators.