The ability of the adult pancreas to generate new insulin (β) cells has been controversial because of difficulties in unequivocally identifying the precursor population. We recently determined that β cells were generated during development from precursors that expressed the homeodomain-containing transcription factor pancreas duodenum homeobox gene-1 (PDX-1). To investigate whether PDX-1⁺ stem cells are present in adult pancreas, we examined two animal models of diabetes. One model was produced by injecting adult mice with streptozotocin (SZ), a toxin that produces hyperglycemia due to rapid and massive β cell death. After SZ-mediated elimination of existing IN⁺/PDX-1⁺ cells, a population of somatostatin (SOM)⁺/PDX-1⁺ cells, a cell type thought to represent an embryonic islet precursor cell, appeared in islets. The appearance of SOM⁺/PDX-1⁺ cells was followed in time by the differentiation to SOM⁺/IN⁺/PDX-1⁺cells. SOM⁺/PDX-1⁺ cells also appeared in islets of nonobese diabetic mice, a strain of mice in which β cell destruction is immune-mediated. Our findings establish the existence of PDX-1⁺ β cell precursors in the adult pancreas and indicate that their differentiation is induced by islet injury .