Transplantation of surrogate β‐cells is a promising option for the treatment of insulin‐deficient diabetes mellitus in the future. Although pancreatic exocrine cells of rodents have been shown to transdifferentiate into insulin‐secreting cells, no studies are reported on human exocrine cells. Here, we report the generation of insulin‐secreting cells from exocrine cells of the human pancreas. When cultured in suspension with epidermal growth factor, human pancreatic exocrine cells readily formed spherical cell clusters. Expression of Pdx1 was induced in all 19 cases in which we successfully isolated exocrine cells, and insulin expression was induced in 11 cases. In addition, insulin secretion was evaluated in four cases, and the newly‐made cells were found to secrete insulin in response to various stimuli. Although further studies are required to improve both the quality and quantity of such insulin‐secreting cells, our data suggest that pancreatic exocrine cells represent a potential source of insulin‐secreting cells for treatment of type 1 diabetes. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00095.x, 2011)