Background & Objectives: Lifestyle changes, such as increasing physical activity and fostering a low–, calorie diet are among the first interventions to reduce body fat and tackle obesity and overweight. Taking supplements, as a simple strategy combined with physical activity may reduce weight, fat, serum lipids, and possibly inflammatory factors. An effective relevant supplement is Royal Gel Supplement (RGS). Recently, using exercise and nutritional supplements to improve physical health has been welcomed,consuming oral supplements is better appreciated, because of their low cost and no adverse effects. However, using supplements, especially RGS along with exercise has ambiguous aspects,limited studies investigated the response of inflammatory markers to aerobic exercise and RJ supplementation. The present study explored the impact of an 8–, week aerobic exercise plus RJS on some inflammatory markers in overweight women. Methods: This was a quasi–, experimental study with a pretest–, posttest and a control group design. Thirty healthy overweight female students of the Islamic Azad University of Sanandaj City, Iran, were selected and randomly divided into (supplement+aerobic training,S+AT), (placebo+aerobic, training,P+AT), and control groups. The subjects were included in the study according to a researcher–, made questionnaire and the inclusion criteria. The inclusion criteria of the study were presenting overweight per body mass index standards and not participating in training programs ≥, 6 months before this study. The exclusion criteria included no systemic problems, no diabetes, no acute or CHRONIC cardiovascular diseases, not receiving pharmacotherapy for the past 3 months, and no smoking. One hour before each training session, the S+AT group received RJS (500 mg) orally in 100mg capsules. The P+AT group, like the supplement group, consumed capsules of the same form and color (containing starch powder) an hour before each training session. However, the controls received no supplement. The 8–, week aerobic training was performed in 3 weekly sessions. Exercise intensity initiated with 60% of Maximal Heart Rate (MHR) in the first week,according to the principle of overload, it reached 75% of MHR by week 8. The required blood samples were obtained from the study subjects at 8 AM by a laboratory expert and CRP, TNF–, α, , and IL–, 6 were measured at pre–,and post–, training in a fasting state. TNF–, α,and IL–, 6 levels were determined by ELISA using the IBL kit according to the manufacturer's instructions (Sigma Aldrich). CRP level was determined by latex–,amplified immunoturbidimetry method (CRPLX Roche Cobas c 501) with a dispersion coefficient of 0. 1 and sensitivity of 0. 3–, 350 mg/L (Pars Azmoon Company Kit). Considering the research design and previous studies’,data, a significance level of 0. 05 was considered. The collected data were analyzed using Analysis of Covariance (ANCOVA) and Bonferroni posthoc tests in SPSS. Results: The achieved results suggested a significant difference in IL–, 6 (p<0. 001). Bonferroni posthoc test data revealed that in IL–, 6, this significant difference concerned the groups supplement with placebo (p<0. 001), supplement with control (p=0. 009), and placebo with control (p=0. 001). There was also a significant difference in the CRP variable (p=0. 030). The results of the Bonferroni posthoc test indicated that in CRP, this significant difference respected the groups supplement with placebo (p<0. 001), and placebo with control (p=0. 040), and supplement with control (p=0. 015). Furthermore, there was a significant difference in TNF–, α,levels between the study groups (p=0. 040). Bonferroni posthoc test data signified that this significant difference belonged to the groups supplement with placebo (p<0. 001) and the supplement with control (p=0. 022). Moreover, 70% of IL–, 6 changes were due to aerobic exercise (Partial Eta=0. 70),55. 9% of CRP changes were induced by aerobic exercise (Partial Eta=0. 559),43. 5% of TNF–, α,changes belonged to aerobic exercise (Partial Eta=0. 435). Conclusion: According to the obtained results, an 8–, week aerobic training plus RJS could reduce the levels of inflammatory markers, including tumor necrosis factor–, alpha, interleukin–, 6, and reactive protein–, C.