ABSTRACT: BACKGROUND:A lack of neurotrophic support is believed to contribute to the development of diabetic neuropathy. On the other hand, neurotrophins have consistently been shown to increase in the central and peripheral nervous system following exercise, but the effects of exercise intervention on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in diabetic neuropathy are not understood. OBJECTIVES:This experimental study was designed and carried out at the Tarbiat Modares university (TMU) in Tehran, Iran, to investigate the hypothesis that increased activity as endurance training can help to increase the endogenous expression of neurotrophins in diabetic rats. METHODS:This was an experimental study with 2 × 2 factorial plans performed at TMU in Iran. Sampling was accidental and 28 adult male Wistar rats in the body mass range of 326.3 ± 8.4 g comprised the sample, with each rat randomly assigned to four groups: diabetic control (DC), diabetic training (DT), healthy control (HC), and healthy training (HT). To induce diabetic neuropathy, after 12 hours of food deprivation, an intraperitoneal injection of streptozotocin (STZ) solution (45 mg/Kg) method was used. Two weeks after STZ injection, the endurance training protocol was performed for 6 weeks; 24 hours after the last training session, the rats were sacrificed. Real-time PCR was used for BDNF and NGF expression. RESULTS:The data indicate that diabetes decreases BDNF and NGF expression in sensory (92%, P = 0.01; 90%, P = 0.038, respectively) and motor (93%, P = 0.05; 60%, P = 0.029, respectively) roots. However, NGF mRNA levels in the DT group were significantly higher than in the HC group ((7.1-fold), P = 0.01; (2.2-fold), P = 0.001, respectively, for sensory and motor roots), but this was not shown for BDNF. In addition, endurance training can increase NGF expression in healthy rats ((7.4-fold), P = 0.01; (3.8-fold), P = 0.001, respectively, for sensory and motor roots). CONCLUSIONS:This study shows that BDNF and NGF expression decreases in diabetic neuropathy. However, this decrease can be reversed through endurance training. These results also indicate that endurance training may have a potential role in compensating for neurotrophin deficiency following diabetic neuropathy.