Introduction: Cell adhesion molecules and inflammation mediators ramp up the activities of vascular endothelial, and researchers consider them as new predictive markers in cardiovascular diseases. With decreasing inflammation, physical 280 Seyyed Mahmoud Hejazi et al. activity can reduce coronary heart disease (CHD) risk. The study was aimed to investigate the effect of one period of selective aerobic training on serum levels of ICAM-1, VCAM-1, and E-selectin in middle-aged women. Methods: Twenty-four healthy middle-aged women participated in this quasi-experimental research. They were equally divided into two groups, control group and experimental group. Subjects in experimental group performed exercise training at increasing intensity of 50 to 75% of their maximum heart rate for eight weeks and three sessions per week for 40 minutes. Blood samples were drawn from both groups twice (24 hours before and 24 hours after the training) in order to measure the intended factors. Paired sample t-test was used to compare the pre-test and post-test data. In order to test the difference between the two groups, independent t-test was used at a significant level (P<0.05). Normality of the data was checked by using the Kolmogorov Smirnov test. Results: Significant difference in the pre-test and post-test mean score of control and experimental groups was observed in serum levels of ICAM-1 and E-selectin (p = 0.005 and p = 0.045 respectively), whereas no change was observed in VCAM-1 level (p = 0.093). Conclusion: The results of the current study indicated that a regular aerobic exercise training while applying overload principle and intensity decreases inflammatory markers related to the incidence, prevention, and control of the cardiovascular diseases, and also reduces the risk for atherosclerosis.