Introduction: The aim of this study was to investigate the effects of iso-caloric combinations of exercise and caloric restriction on insulin sensitivity of obese male rats. Materials and Methods: Fifty-six, eight-week-old male Wistar rats (190±16 g) were primarily divided into the obesity (n=48) and healthy groups (n=8) and were fed high-fat and standard palate for seventeen weeks respectively. After obesity induction, the obesity group was randomly assigned to one of six groups, i.e. EXE, CR, EXCR1, EXCR2, and EXCR3 as experimental groups and OC as the control group following which 15% of food intake was reduced. Their exercise intensity was about 70-75% vo2max, 28 m/min for 48 to 55 minutes. Negative energy balance was applied through caloric restriction (CR) (6d/w); exercise training (EXE) (6d/w), in three combinations: EXCR1 (2d/w exercise + 4d/w CR, (EXCR2 (3d/w exercise + 3d/w CR) and EXCR3 (4d/w exercise + 2d/w CR) for two months. One way ANOVA and Tukey post-hoc were applied for data analysis by SPSS version 16 (p<0.05). Results: Serum glucose levels of EXE, CR, EXCR1, EXCR2 and EXCR3 significantly decreased compared to the OC group. Plasma CR and EXCR3 insulin were significantly decreased, in comparison to OC insulin level. Compared to OC, insulin sensitivity was significantly elevated in CR and EXCR2. Conclusion: It is concluded that exercise and caloric restriction, both per se and in different combinations reduced obesity elevated induced serum glucose. However caloric restriction and EXCR2 and caloric restriction lead to significant increase in insulin sensitivity. It is recommended to consider equal doses of exercise and caloric restriction which may improve insulin sensitivity.