The chemokine receptor CXCR4 and ligand SDF-1alpha are expressed in fetal and adult mouse islets. This work details how expression of CXCR4, a marker of definitive endoderm in hESC differentiation of cells towards cells of endocrine lineage, is expressed exclusively with Ngn3+ and insulin producing cells in both human fetal pancreatic cells and human adult islets. Furthermore, we demonstrate that CXCR4 and its ligand SDF1α (expressed in ductal cells) is absolutely required generation of insulin producing cells.