Pancreatic exocrine cells can be directly converted to insulin(+) beta cells by adenoviral-mediated expression of three transcription factors Pdx1, Mafa, and Ngn3 in the adult mouse pancreas (Zhou et al., Nature 455(7213):627-632, 2008). This direct reprogramming approach offers a strategy to replenish beta-cell mass and may be further developed as a potential future treatment for diabetes. Here, we provide a detailed protocol for inducing exocrine to beta-cell reprogramming in mice. We also describe key analyses we routinely use to assess the phenotype and function of reprogrammed cells.