Aim To investigate the role of miR-21/PTEN/Akt signal pathway in resveratrol promoting angiogenesis of endothelial progenitor cells(EPC) isolated from rat bone marrow. Methods Mononuclear cells were isolated by density gradient centrifugation from rat bone marrow and then cultured with EGM-2MV containing 10% fetal bovine serum. 3～5 generations of EPC were used in the experiments. EPC were treated with resveratrol (20 μmol/L) for 12 h.And then matrigel, real-time PCR and Western blot were used to detect the angiogenesis, the expression of miR-21 and PTEN mRNA , and the PTEN protein and Akt phosphorylation level of EPC in vitro separately. The dual luciferase reporter system was employed to detect the binding of miR-21 and PTEN mRNA. Results Resveratrol (20 μmol/L) significantly promoted the angiogenesis of EPC in vitro (P＜0.05). In the meantime, resveratrol inhibited the expression of miR-21 which promoted the gene and protein expression of PTEN. PTEN furtherly inhibited the phosphorylation level of Akt. The results of the double luciferase reporter system showed that miR-21 bound to the 3′UTR of PTEN mRNA.Conclusion miR-21 regulated the angiogenesis ability of EPC promoted by resveratrol. The present study indicated that miR-21/PTEN/Akt signaling pathway may play an important role in EPC angiogenesis promoted by resveratrol in vitro.