Background: The purpose of this study was to investigate the effect of saffron (Crocus speciosus) supplementation following high-intensity exercise training on serum levels of vascular endothelial growth factor (VEGF) and endostatin in patients with coronary artery bypass graft surgery (CABG).Methods: This was an applied quasi-experimental study. Participants were 40 patients who had been under surgery at least one month before this study; after screening, they were selected and randomly assigned to 3 groups. High-intensity interval training (HIIT) group in each session performed two 10-minute sets (15 seconds of activity with 100% peak power, and 15 seconds of inactive breaks and 4 minutes of rest between two 10-minute intervals), and the supplementary training group digested a daily 300-mg of saffron supplement behind training like the high-intensity interval training group. Vascular endothelial growth factor and endostatin were checked before and after training and supplement intervention. ANOVA and Bonferron's post hoc test were used to identify any diffrence. All statistical analyzes were performed at significance level of P < 0.05.Findings: Serum vascular endothelial growth factor and lef ventricular ejection fraction (LVEF) increased, and endostatin decreased in both training and supplementary training groups comparing to controls (P < 0.05).Conclusion: In this study, it was found that high-intensity interval training with increase in endothelial growth factor, and reduction in serum level of endostatin, is effective in improving angiogenesis, and suppressing angiogenesis inhibitors in patients after coronary artery bypass graft surgery.