Introduction and Objective: Melanocortin 4 receptor plays a key role in regulating appetite and energy balance, while leptin acts as a satiety hormone and is effective in weight control. Dysfunction in their activity has been linked to obesity and metabolic disorders. The study investigated the effects of Electrical Muscle Stimulation training on serum levels of MC4R and leptin in obese men. Materials and Methods: This semi experimental study was conducted on 30 obese men (aged 30–40) in Shiraz, randomly assigned to two groups: EMS and control (15 participants each). The EMS group underwent a standard EMS protocol, three sessions per week for 20 minutes each, over 8 weeks. Blood samples were collected before and after the intervention; serum levels of MC4R and leptin were measured using ELISA. Data were analyzed with SPSS version 22 using the Shapiro–Wilk test, ANOVA, and paired t test (P ≤ 0.05). Results: The results showed that EMS training led to a significant increase in serum MC4R levels (P = 0.001) and a significant decrease in serum leptin levels (P = 0.001) in the EMS group compared to control. Further analysis confirmed a strong effect size for these changes (P = 0.001). Conclusion: These findings suggest that EMS training can serve as an effective therapeutic approach in improving metabolic profiles, regulating appetite, and managing weight in obese men. The impact of EMS on MC4R and leptin levels holds clinical potential. However, further studies with larger sample sizes and longer follow up periods are needed to confirm these results.