Introduction: The purpose of this study was to investigate the effects of high intensity interval training (HIIT) and moderate intensity continuous training (MICT) on irisin, FGF-21 and insulin resistance in obese male rats. Material and Methods: Forty male rats were divided into two groups: high-fat diet (n=32) and standard diet (n=8), for 10 weeks. After inducing obesity, eight rats from the high-fat diet group (O) and eight  from the standard dietary group (C) were sacrificed, and the other obese rats were randomly divided into three groups: obesity control (OC), moderate intensity continuous training (MICT) and high intensity interval training (HIIT). The HIIT protocol, including 10 bouts of 4-minute activity with equivalent intensity of 85-90% vo2max and 2 minute active rest periods, and the MICT protocol with equivalent intensity of 65-70% VO2max, with covered distance matched to that of the HIIT protocol, were performed for 12 weeks and 5 sessions per week. Serum samples were collected in two steps (after completion of diet and training protocols) to measure serum levels of irisin, FGF-21, insulin and glucose by ELISA. Results: In the comparison of the HIIT group to the OC group, serum levels of irisin (6.43 ±0.93 ng/ml vs. 4.61±0.61 ng/ml, p=0.003) and FGF-21 (1658±206.5 ng/l vs. 1093±125.97 ng/l, P=0.007) significantly increased, while MICT had no significant effect on these two hormones (P=0.29, P=1.00 respectively). Also, when comparing both the HIIT and MICT groups to the OC group, serum levels of glucose (HIIT: 111.16±4.07 mg/dl, MICT: 117.5±1.37 mg/dl vs. 154.66±13.21 mg/dl, P=0.001, P=0.001 respectively) and insulin resistance index (HIIT: 1.96±0.20, MICT: 2.53±0.46 vs. 3.89±0.54, P=0.001, P=0.01 respectively) significantly decreased; although, serum insulin reduction (1.49±0.15 ng/ml vs. 2.14±0.43 ng/ml, P=0.018) was only significant in the HIIT group (P=0.018). Conclusion: It seems that both HIIT and MICT training protocols lead to improved insulin resistance in obese rats. However the increase in serum irisin and FGF-21 was significant only in the HIIT group, suggesting that exercise intensity plays an important role in regulating the secretion of these hormones.