Purpose : Atherosclerosis is a complex multifactorial disease whose first steps can be initiated from childhood. Therefore, we examined the effects of 2 training models on salusins levels, inflammatory markers, and lipid profile in boys with overweight/obesity. Method : Forty-five boys with overweight/obesity with the mean age of 11.06 (1.0) years were randomly divided into three groups of 15: a high-intensity interval training (HIIT) group (100%–110% of maximum aerobic speed); an aerobic training group (40%–70% of heart rate reserve); and a control group. The intervention included 3 sessions per week for 12 weeks. Results : Findings showed significant improvements in serum levels of salusins, salusins ratio, interleukin-6 (IL-6), and total cholesterol (TC) in both training groups ( P  < .001). Also, the serum levels of C-reactive protein (CRP), triglycerides (TG), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), atherogenic index of plasma (AIP), and cholesterol index improved significantly ( P  < .01). Except for the TG, HIIT caused higher improvements than aerobic training ( P  < .001 for salusin-α, salusins ratio, IL-6, CRP, TC, HDL, AIP, and cholesterol index; and P  < .01 for salusin-β and LDL). Conclusion : The present study shows that HIIT has more positive effects than aerobic exercise on the atherosclerotic and inflammatory factors, as well as lipid profile variables in children with overweight/obesity.