Regenerative medicine,including cell-replacement strategies,may have an important role in the treatment of type 1 diabetes which is associated with decreased islet cell mass.To date,significant progress has been made in generating insulin-secretingβcells from pluripotent mouse embryonic stem cells(ESCs).The aim of this study is to explore the potential of regulating the differentiation of ESCs into pancreatic endocrine cells capable of synthesizing the pancreatic hormones including insulin,glucagon,somatostatin and pancreatic polypeptide under proper conditions. Undifferentiated ES cell line was stably transfected with mouse RIP-YFP plasmid construction in serum-free medium using Lipofectamine~(?) 2000 Reagents.We tested pancreatic specific gene expression and characterized these ESC-derived pancreatic endocrine cells.Most of these insulin-secreting cells co-expressed many of the phenotypic markers characteristic ofβcells such as insulinl,insulin2,Isletl,MafA,insulinoma-associated antigen 1(IA1) and so on,indicating a similar gene expression pattern to adult islet p cells in vivo.Characterization of this population revealed that it consisted predominantly of pancreatic endocrine cells that were able to undergo pancreatic specification under the appropriate conditions.We also demonstrated that zinc supplementation mediated up-regulation of insulin-secreting cells as an effective inducer promoted the development of ESC-derived diabetes therapy.In conclusion,this work not only established an efficient pancreatic differentiation strategy from ESCs to pancreatic endocrine lineage in vitro,but also leaded to the development of new strategies to derive transplantable islet-replacementβcells from embryonic stem cells for the future applications of a stem cell based therapy of diabetes. Regenerative medicine, including cell-replacement strategies, may have an important role in the treatment of type 1 diabetes which is associated with decreased islet cell mass. To date, significant progress has been made in generating insulin-secreting cells from pluripotent mouse embryonic stem cells ESCs). The aim of this study is to explore the potential of regulating the differentiation of ESCs into pancreatic endocrine cells capable of synthesizing the pancreatic hormones including insulin, glucagon, somatostatin and pancreatic polypeptides under proper conditions. Undifferentiated ES cell lines were stably transfected with mouse RIP-YFP plasmid construction in serum-free medium using Lipofectamine® 2000 Reagents. We tested pancreatic specific gene expression and characterized these ESC-derived pancreatic endocrine cells. Host of these insulin-secreting cells co-expressed many of the phenotypic markers characteristic of βcells such as insulinl, insulin2, Isletl, MafA, insulinoma-associated an tigen 1 (IA1) and so on, indicating a similar gene expression pattern to adult islet p cells in vivo. Characterization of this population that that consisted predominantly of pancreatic endocrine cells that were able to undergo pancreatic specification under the appropriate conditions. We also demonstrated that zinc supplementation mediated up-regulation of insulin-secreting cells as an effective inducer promoted the development of ESC-derived diabetes therapy. conclusion, this work not only established an efficient pancreatic differentiation strategy from ESCs to pancreatic endocrine lineage in vitro, but also leaded to the development of new strategies to derive transplantable islet-replacementβcells from the embryonic stem cells for the future applications of a stem cell based therapy of diabetes.