E2 (oestradiol-17β) is an important hormone that regulates various cell functions including insulin production. hIPCs (human islet-derived precursor cells) are capable of proliferating and differentiating into cells that secrete insulin in response to glucose in vivo and in vitro. However, the effect of E2 on hIPCs is currently unclear. In this study, we found that ERα (oestrogen receptor alpha), but not ERβ, was expressed on hIPCs, and E2 promoted the proliferation and inhibited the differentiation of adult hIPCs. Although fetal hIPCs also express ERα, no effect of E2 on the fetal hIPCs was observed, suggesting differing roles of E2 at different stages of pancreatic development. This study indicates that E2 may be one of the key factors that control the turnover of adult pancreatic β cells by regulating the proliferation and differentiation of adult hIPCs through ERα.