Background: New pieces of evidence show that the leptin released from adipose tissue is associated with obesity; however, leptin response to different types of exercise programs in humans is unknown. Objectives: The aim of this study was to compare the effects of aerobic versus resistance training on serum leptin and insulin resistance in sedentary men.Methods: Thirty male volunteers with a mean age of 23.2 ± 1.23 years, body mass index (BMI) 23.9 ± 0.95 kg.m -2 , fat percent 18.28 ± 1.15, and waist-to-hip ratio 0.89 ± 0.02 were randomly assigned into three groups, including aerobic, resistance exercise, and control groups (n = 10). The resistance exercise program was performed for 60 minutes at 70% of one repetition maximum for 3 sets. Every set consisted of 10 repetitions per move (RPM) followed by a 30-second-rest interval between every station accompanied by a 2-minute-rest between every set. The aerobic exercise program consisted of running on a treadmill for 30 minutes at 60 to 70 percent of reserved heart rate (maximum heart rate-heart rate rest). Fasting blood samples were collected before and after 6 weeks after the termination of the exercise protocol in order to determine the plasma leptin level and insulin resistance. Results: The results of one-way ANOVA showed that body fat percentage and waist-to-hip ratio were significantly decreased in both experimental groups and maximum aerobic power and one repetition maximum of bench press plus leg press were significantly increased (P < 0.05). In addition, insulin resistance levels were significantly decreased in both exercises groups compared with the control group. However, the leptin level was significantly decreased in the aerobic exercise group compared with the other two groups (P < 0.05). Conclusions: According to these findings, both aerobic and resistance training without changes in body weight and body mass index appear to be a non-prescriptive therapeutic approach to lower the insulin levels and insulin resistance in sedentary men. However, aerobic versus resistance training may play a role in regulating systemic leptin.