Objective：To explore the synergistic effects and related mechanisms of brain-derived neurotrophic factor（BDNF） on aerobic exercise-induced angiogenesis and improved cardiac function. Methods：In the in vitro experiments，human umbilical vein endothelial cells（HUVECs） were exposed to 12 dyn/cm2 laminar shear stress（LSS） in parallel-plate flow chamber to mimic the effects of exercise training on vascular tissue. BDNF/TrkB protein expression levels in HUVECs treated by non-circulating flow，circulating flow，circulating flow with BDNF（50 ng/mL） were examined by Western blot，meanwhile phosphorylated TrkB and Akt protein levels were also analyzed；the capacities of cell migration and tube formation were analyzed to evaluate the angiogenesis of HUVEC. In the in vivo experiments，sixty rats were assigned to sham group，myocardial infarction（MIC） group，myocardial infarction+BDNF（MICB） group，myocardial infarction+exercise（MIE） group and myocardial infarction+exercise+BDNF（MIEB） group；cardiac functional was evaluated prior to exercise training and 1 week after cardiac surgery. the exercise groups were subjected to 4 weeks of treadmill running，the MIEB group subjected to exercise and daily tail intravenous injection of rhBDNF at a dose of 0.4 μg/kg 10 minutes before exercise，the MICB group subjected to the same dose of rhBDNF only. The rats underwent cardiac functional evaluations following the 4-week period of exercise training. The blood vessel density in the surrounding area of myocardial infarction was detected by immunohistochemistry after the 4-week period of training. Results：An increased BDNF protein expression，as well as phosphorylated of TrkB and Akt levels were observed in HUVECs exposed to LSS generated by circulating fluid. LSS elicited sustained increase BDNF level in the circulating medium. In HUVECs exposed to LSS generated by non-circulating fluid， an increased BDNF protein expression was also observed，while the TrkB and its downstream Akt pathway were inactive. Circulating fluid with BDNF could increase the TrkB and Akt phosphorylated degree and improve the angiogenesis ability of HUVECs. The in vivo experiments confirmed that BDNF administration in rats combined with aerobic exercise increased myocardial angiogenesis and improved cardiac function more significantly compared with those rats receiving exercise intervention only. Conclusion：Exercise activates BDNF/TrkB axis and its downstream Akt pathway through LSS in a BDNF-dependent manner， thereby enhancing cell migration and tubule formation；exogenous supplementation of BDNF in association with aerobic exercise may enhance the pro-myocardial angiogenesis effect of exercise and further improve cardiac function.