Introduction: Bone marrow derived progenitor cells (BMPCs) are potential candidates for autologous cell therapy in tissue repair because of their high angiogenic potential. However, increased progenitor cell apoptosis in diabetes directly limits their success in the clinic. MicroRNAs are endogenous non-coding RNAs that regulate gene expression at the post-transcriptional level, but their roles in BMPC-mediated angiogenesis are incompletely understood. In the present study, we tested the hypothesis that the pro-angiogenic miR-27b inhibits BMPC apoptosis in type 2 diabetes. Methods and Results: Bone marrow-derived EPCs from adult male type 2 diabetic db/db mice and control db/+ mice were used. MiR-27b expression (real-time PCR) in EPCs was decreased after 24 hours of exposure to methylglyoxal (MGO) or oxidized Low-Density Lipoprotein. The increase in BMPC apoptosis in the diabetic mice or under MGO exposure was rescued by miR-27b mimic. p53 and the Bax/Bcl-2 ratio in EPCs (Western blot analyses) were significantly higher in diabetic BMPCs, both of which were suppressed by miR-27b. Furthermore, mitochondrial respiration as measured by oxygen consumption rate was enhanced by miR-27b in diabetic BMPCs, with concomitant decrease of mitochondrial Bax/Bcl-2 ratio. The 3'UTR binding assays revealed that both Bax and its activator RUNX1 were direct targets of miR-27b, suggesting that miR-27b inhibits Bax expression in both direct and indirect manners. Conclusion: miR-27b prevents EPC apoptosis in type 2 diabetic mice, at least in part, by suppressing p53 and the Bax/Bcl-2 ratio. These findings may provide a mechanistic basis for rescuing BMPC dysfunction in diabetes for successful autologous cell therapy.