Abstarct: Introduction & Objective: Lifestyle changes have driven modern societies toward weight gain and obesity as far as the phenomenon is pandemic. Serotonin is one of the neurotransmitters involved in the process of weight gain and obesity; so that increasing its levels consistent with exercise can significantly reduce appetite and weight control. The aim of this study was to investigate the response of serotonin to different intensities of one-session aerobic exercise in overweight and obese girls. Methodology: The subjects consisted of 40 overweight and obese girls with a mean age of 21-19 years who were randomly selected into four groups of 10 (experimental group 1, experimental group 2 , Experimental group 3 and control group). The training program of the experimental groups with three intensities of 40%, 60% and 80% of the peak oxygen consumption (VO2peak), running on the treadmill. Blood samples were taken at rest and after 12 hours fasting and immediately after exercise. The measured variables included serotonin and lipid profiles (LDL, HDL, TG, TC). The statistical significance level (P <0.05) was determined. Data were analyzed using SPSS software version 21. Results: According to ANOVA, an aerobic exercise session with different intensities significantly increased serotonin levels in experimental group 2 and experimental group 3 compared to the control group (P <0.05) While lipid profiles did not change significantly in any of the experimental groups compared to the control group (P> 0.05). Conclusion: The results of this study showed that acute aerobic exercise with intensity of 60% and 80% of maximum oxygen consumption can improve blood serotonin levels and serve as an effective weight control strategy in the field of non-pharmacological treatments.