Myoglobinuric acute kidney injury (MAKI) is a uremic syndrome that develops after a damage in the skeletal muscle cells and passing into the intracellular components of the cells to the circulation, rhabdomyolysis, with traumatic or non-traumatic reasons. In this study, we aimed to investigate of the role of irisin that produced by the skeletal muscle, on physiopathology of experimental MAKI. In the study, 42 Sprague Dawley male rats which were 170-200 g weight were used. Rats were deprived of water for 24 hours. The control groups (groups 1, 3 and 5, n=6) were received saline solution (8 ml/kg) and the MAKI groups (group 2, 4 and 6, n=8) were received intramuscular 50% glycerol solution (8 ml/kg). The rats in group 1 and 2 after 6 hours, rats in groups 3 and 4 after 24 hours, rats in groups 5 and 6 after 48 hours of intramuscular injection were sacrificed under anaesthesia. The blood samples were taken and kidneys tissues of the animals were removed. Urine samples were collected for 24 hours. We examined kidney irisin expression immunohistochemically and plasma/urine irisin concentrations using an ELISA system. Values are means ± SD., compared by Mann-Whitney U test.There was a significant increase in plasma irisin levels between 5th and 6th groups (235,27±38,36 vs 289,05±39,16, p<0,05) and between 4th and 6th groups (237,26±37,14 and 289,05±39,16, p<0,05). There was a significant decrease in the urine irisin levels between 3th and 4th groups (213,40±17,39 vs 42,93±17,00, p<0,05) and between 5th and 6th groups (161,75±42,07 vs 29,61±11,57, p<0,05). There was not a significant increase in the kidney tissue irisin expression immunohistochemically between 1st and 2nd groups (275,00±12,25 and 255,00±22,68 p>0,05). On the other hand, there was a significant decrease between 3th and 4th groups (275,00±22,58 and 176,25±15,06 p<0,05), between 5th and 6th groups (270,00±18,98 and 101,25±20,31, p<0,05). For the renal injury score, there was a significant increase between 1st and 2nd groups (0,17±0,41 vs 1,88±0,35, p<0,05), between 3rd and 4th groups (0,17±0,41 vs 2,63±0,52 p<0,05), between 5th and 6th groups (0,17±0,41 vs 3,75±0,46 p<0,05). There was a significant increase in serum urea, creatinine, potassium levels, alanine transaminase, aspartate transaminase, lactate dehydrogenase, creatine kinase activities between control and MAKI groups (p<0,05). We observed a time-dependent degradation in the kidney function and increase in the histopathological damage. While there was a decrease in the urinary irisin levels and kidney tissue irisin expression, serum irisin levels were increased depending on the time basis. These findings suggest that irisin might be used as a diagnostic marker in the pathogenesis of MAKI.