It is an object of the present invention to provide a method for efficiently directing differentiation into insulin-producing cells in a xeno-free culture system. According to the present invention, there is provided a method for directed differentiation into insulin-producing cells, comprising culturing stem cells in the following steps (1) to (5): (1) a step of culturing stem cells in a medium comprising an activator of activin receptor-like kinase-4/-7 and a GSK3 inhibitor and then culturing in a medium comprising an activator of activin receptor-like kinase-4/-7 (2) a step of culturing the cells obtained in step (1) in a medium comprising a hedgehog signaling inhibitor and an FGF (3) a step of culturing the cells obtained in step (2) in a medium comprising a retinoic acid receptor agonist, a hedgehog signaling inhibitor and a BMP signaling inhibitor (4) a step of culturing the cells obtained in step (3) in a medium comprising a TGF-β type I activin receptor-like kinase-4/-5/-7 inhibitor and a BMP signaling inhibitor and (5) a step of culturing the cells obtained in step (4) in a medium comprising a phosphodiesterase inhibitor.
