In the present study, we investigated whether Tat-CIAPIN1 protein could protect against cytotoxic effects of hIAPP, in vitro β-cell and in vivo T2DM animal model, and we observed that this fusion protein protected against hIAPP-induced cell death in RINm5F cell, as well as in pancreatic β-cell of the HFD combined with STZ-induced T2DM mouse model. Here, CIAPIN1 is linked to type 2 diabetes mellitus.