Introduction: High-fat diet intake leads to diet-induced obesity in concert with multiple cardiovascular risk factors such as metabolic syndrome and apoptosis. The aim of this study was to evaluate the effects of aerobic training with along capsaicin on cardiac apoptosis regulator BAX (Bax), B-cell Lymphoma 2 (Bcl2) and Bax/Bcl2 in rat fed a high-fat diet (HFD). Materials and Methods: 40 male Wistar rats were fed a normal diet (ND, n = 8) or HFD (n = 32) for 8 weeks. After 8 weeks, all rats were divided into 5 groups: ND, HFD, high-fat diet-training (HFDT), high-fat diet-capsaicin (HFDCap), high-fat diet-training-capsaicin (HFDTCap). Training groups have performed a progressive aerobic running program (at 15-25 m/min, 30-60 min/day, and 5 days/week) on a motor-driven treadmill for eight weeks. Capsaicin (4 mg/kg/day) were administered orally, by gavage, once a day. Results: The results of this study showed that Bax and Bax/Bcl2 in HFDT (Respectively p=0. 016, p=0. 000), HFDCap (Respectively p=0. 014, p=0. 000) and HFDTCap (Respectively p=0. 000, p=0. 000) groups was significantly decreased compared to HFD. Bax and Bax/Bcl2 in HFDTCap was significantly decreased compared to HFDT (Respectively p=0. 034, p=0. 033) and HFDCap (Respectively p=0. 038, p=0. 036) groups. Also, Bcl2 significantly increased in to HFDT (p=0. 001) and HFDCap (p=0. 000) and HFDTCap (p=0. 000) groups compared to HFD. Conclusion: Exercise and capsaicin improve the apoptosis induced by obesity, and suggest that exercise and capsaicin can be considered as an excellent candidate for therapy of these clinical conditions.