Abstract : Irisin was found in cerebrospinal fluid and the paraventricular nucleus in humans suggesting that it has central as well as peripheral metabolic functions. No data available demonstrating the effect of upper or lower motor neuron lesion on irisin levels. We hypothesized that irisin levels are changed after motor neuron lesion and these changes are correlated with body weight changes observed after UMNL or LMNL. 40 male rats were divided into 4 groups; control for UMNL, UMNL group, control for LMNL and LMNL group. Body Weight (BW), Body mass index (BMI), plasma and muscle tissue irisin levels were measured. Highly significant increases in plasma and muscle tissue irisin levels were found in UMNL and LMNL groups compared with control groups (p≤0.001 and p≤0.05). Significant reductions in BW and BMI were found in UMNL and LMNL groups compared with their control groups (p≤0.05). Also, a significant negative correlation was found between irisin and body weight (r*=- 0.7975, p≤0.05) and body mass index (r*= - 0.9792, p≤0.05) in all groups. We suggested that irisin might have an important role in weight reduction observed UMNL and LMNL