Introduction: Regular exercise training plays an important role in the improvement of metabolic disorders, inflammatory markers and cardiovascular diseases. The purpose of this study was to investigate effect of 19 weeks aerobic exercise on insulin resistance and high sensitive C reactive protein (hs-CRP) levels in middle-aged women. Materials and Methods: Twenty-four sedentary women, (aged 43.3±10.6 years) were randomly the selected from among volunteers. The subjects were assigned to two, the obese (BMI: 32.7±4.8 kg/m2) or the non-obese (BMI: 24.3±1.3 kg/m2) groups. Exercise training consisted of 19 weeks, aerobic and resistance exercises, with a frequency of 3 days a week, and intensity corresponding to 60-80% HRmax for 60-75 minutes per session. Results: After 19 weeks, body mass index (BMI), body fat percent and hs-CRP same as Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index was decreased in the both groups (P<0.05), and the decrease was greater in the obese compared to the non-obese group. Maximal oxygen consumption, also, increased significantly in both groups after exercise (P<0.05). For WBC, HDL-Cand LDL-C, no significant differentces were observed after intervention. Conclusion: It can be concluded that changes in HOMA-IR and hs-CRP levels are due to the improvement of the body health status composition, long duration and anti-inflammatory features of exercise training.