Objective: Islet cell transplantation has been considered as one of the potential approaches for treating Type I diabetes, which is characterized by the loss of pancreatic β-cell function and insulin content. However, its clinical application is hampered by the lack of donor islets, motivating many researchers to study efficient protocols, that use stem cells to differentiate into insulin producing cells (IPCs) as alternative sources of islets. Although many scientific reports raised the possibilities for the clinical application of differentiated IPCs, current IPCs producing protocols are both highly complicated and expensive due to differentiation inducing agents such as cytokines, growth factors, and chemicals etc. Furthermore, the roles of these agents in generating IPCs have not been fully elucidated yet. Such limitations led us to seek novel strategy to secure available IPCs. Methods: β-cell derived microvesicles (β-MVs) themselves direct the differentiation of murine bone marrow derived cells (mBMDCs) into IPCs without any supplements of known differentiation inducing agents. These β -MVs mediated IPCs express murine β-cell specific transcripts and proteins within 7 days. Results: we found mBMDCs can be differentiated into IPCs expressing mouse specific beta cell gene expression (Insulin, PDX-1, MafA, Neurogenin3 etc.) On the contrary, microvesicles from Endothelial cells (non-beta cells) did not affect the β-cell differentiation, suggesting unidentified key components in β-MVs that directly differentiate BMDCs into IPCs instead of simply transferring species specific transcripts or proteins. Moreover, transplantation of premature β-MVs directed IPCs attenuated hyperglycemia in diabetic mice induced by streptozotocin. Conclusion: These results demonstrate that β-MVs contain much more information in IPCs differentiation, which could be applied in treating diabetic patients. This study was supported by a grant from the Innovative Research Institute for Cell Therapy (A062260) and a grant from the Korea Healthcare Technology R&D Project (A120273) by the Ministry of Health and Welfare, Republic of Korea.