We aimed to investigate the contribution of irisin in the neuroprotective process of exercise training in diabetic rats. Serum irisin levels, thermal and mechanical pain thresholds and intracellular calcium ([Ca2+](i)) levels in sensory neurons were measured at different time intervals during the eight weeks of exercise sessions for the control, non-exercise diabetics (3 groups) and exercise performing (low and high intensity groups) diabetic rats (n = 7-10 for all groups). Non-exercise diabetic groups were treated with irisin in different doses (1, 10 and 20 mu g/kg respectively). Recovered pain thresholds at the end of the exercise sessions (p < .05), higher serum irisin levels that compared to control and diabetics (p < .05) and insignificant mean [Ca2(+)](i) peak amplitudes in sensory neurons (p > .05) obtained from experiments. Furthermore, irisin injection decreased the thermal pain threshold of diabetics only at 60th minutes (p < .05). Irisin may have a role in the neuroprotective effect of exercise training.