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Objective: Atherosclerosis is the most common cause of coronary heart disease and a major cause of ischemic heart diseases. We have investigated the effect of eight weeks of aerobic training on the serum levels of leptin, IL-6, and TNF-α in inactive elderly women. Methods: In this semi-experimental study, participants were selected by convenience sampling. We divided 21 subjects into two groups - active (n=10) and non-active (n=11). The program training included 60 min per session, 3 times per week for 8 weeks of aerobic exercise with 50-70 HRR%. Blood samples were taken before and after 8 weeks of aerobic training. We used the t-test for dependent and independent samples for intra- and intergroup comparisons. For all statistical comparisons, the level of significance was set at P<0.05. Results: The aerobic training groups had a significant reduction in leptin (P=0.001), IL-6 (P=0.01), and TNF-α (P=0.001) after 8 weeks of aerobic training compared with the control group. The intergroup variations in weight, BMI, leptin, and TNF-α had a significant change (P<0.05). Conclusion: The results of the present study suggested that endurance training decreased leptin, IL-6, and TNF-α levels, effectively improved cardiovascular health, and reduced the risk of atherosclerosis.