Neurotrophins mediate the effects of physical activity on brain health and function. The aim of this study was to investigate the effect of aerobic exercise in the form of treadmill running with and without carbohydrate supplementation on serum levels of BDNF, NT-3, NT-4 and IGF-1. In this semi-experimental study, 12 beginner adolescent male futsal players in Khorramabad city (age: 17. 13± 0. 64 years; weight: 64. 25± 10. 18 kg; height: 172. 88± 5. 59 cm) were voluntarily selected. Subjects performed 1 hour of running with moderate intensity (60% of heart rate reserve) in two sessions with carbohydrate supplementation or placebo in a randomized cross-over design. Blood samples were obtained before the first session and 5 min. after sessions. The serum levels of BDNF, NT-3, NT-4 and IGF-1 were measured using an ELISA kit. Data were analyzed by repeated measures test and the level of significance was set at P<0. 05. The results showed that 1 hour of treadmill running with and without supplementation could significantly increase serum levels of BDNF, NT-3 and NT-4 compared with the baseline (P<0. 05). Despite more increase in BDNF, NT-3 and NT-4 during supplementation, there was no significant difference between supplementation and placebo (P>0. 05). Also, serum levels of IGF-1 did not change (P=0. 099). One hour of aerobic exercise with moderate intensity with and without carbohydrate supplementation equally increased serum BDNF, NT-3 and NT-4 significantly. Therefore, it seems that duration/intensity of exercise or both or concentration of carbohydrate should increase in order to increase the effects of carbohydrate supplementation on serum levels of neurotrophins.