In the present study, three new lines of evidence reveal the beneficial effects of liraglutide on ischemic angiogenesis in diabetic mice and the angiogenic function of EPC: (1) liraglutide enhances blood perfusion and angiogenesis in the ischemic hindlimb of both T1DM and T2DM mice; (2) liraglutide promotes the angiogenic capability of HG-treated EPC by activating Nrf2, which also restores the eNOS phosphorylation and thereafter NO production of EPC; (3) liraglutide promotes the transcriptional activity of Nrf2 via an AKT-GSK3β-Fyn pathway. Here, AKT1 is linked to type 1 diabetes mellitus.