Introduction: Leptin is a polypeptide produced by many cells, including adipocytes and appetite regulation is one of the most important functions. This hormone is a molecule with high potential to participate in a wide range of physiological and pathological functions that increase during pregnancy. During labour, leptin levels increase significantly, which can explain the difference between maternal serum leptin levels in  vaginal delivery and cesarean section. Therefore, In this study, we compared maternal serum leptin levels during the third trimester of pregnancy and postpartum in the two groups of women delivered by vaginal delivery and caesarean section. Materials and Methods: In this a nested case-control study of 166 pregnant women, maternal serum leptin levels at 28-32 weeks gestation and the first 24 hours after birth were measured. Data were analyzed by using the t-test, Fisher and Chi-square tests. Results: Test results indicated a significant difference in serum leptin levels in both women before and after vaginal delivery and elective caesarean delivery (P>0.001) and (P=0.004) respectively. Maternal serum leptin levels in the first 24 hours after birth in the two groups showed significant difference (P>0.001). Conclusion: Maternal serum leptin levels were significantly higher after vaginal delivery than after cesarean section. Given the widespread effects of leptin on maternal and neonatal outcomes, vaginal delivery is recommended as the preferred method.