en فیزیولوژی ورزشی Sport Physiology تحقيقي Original Paper <strong>Background and objectives</strong>: It has been suggested that irisin and fibronectin type III domain-containing protein 5 (FNDC5) can increase energy expenditure, promote weight loss and improve insulin resistance in diabetic patients by affecting white and brown adipose tissues. In this study, we investigate effect of adipose tissue-derived stem cell transplantation and six weeks of aerobic exercise on FNDC5 and irisin levels in streptozotocin-induced diabetic rats.<br> <strong>Methods:</strong> Forty-eight rats (weighing 220-240 g and aged nine weeks) were divided into six groups of control, sham, diabetes control, diabetes + exercise, diabetes + stem cell and diabetes+ exercise + stem cell. The exercise group ran on running wheel at intensity of 60-70% VO₂max, five days a week for six weeks. Next, 1.56 &times; 10⁶ stem cells extracted from human adipose tissue were injected into the tail vein of streptozotocin-induced diabetic rats. Finally, FNDC5 and irisin plasma levels of the mice were measured using enzyme-linked immunosorbent assay kits. &nbsp;<br> <strong>Results: </strong>FNDC5 and irisin levels reduced significantly in the diabetes control group (P=0.0001). FNDC5 levels in the diabetes + exercise + stem cell and the exercise group increased significantly compared to the diabetes control group (P=0.0001). The irisin level in the diabetes + stem cell + exercise group, exercise group and stem cell group increased significantly compared to the diabetes control group (P=0.0001). &nbsp;<br> <strong>Conclusion:</strong> The results indicate that aerobic exercise program and stem cell therapy alone and combined can significantly increase plasma irisin levels. Given the favorable effects of adipose tissue-derived stem cell injection and aerobic exercise on FNDC5 and irisin levels, this strategy could be further evaluated in coping with the adverse effects of diabetes on metabolism and aging Aerobic exercise, Adipose tissue-derived stem cell, FNDC5, Irisin, Diabetes 34 40 http://mlj.goums.ac.ir/browse.php?a_code=A-10-937-1&slc_lang=en&sid=1 mehdi nasiraey mehdi.nasiraey@gmail.com 100319475328460018365 100319475328460018365 Yes Department of Sport Physiology Abdolreza Jafari chashmi Jafarychashmy@gmail.com 100319475328460018366 100319475328460018366 No Department of Sport Physiology, Sari Branch, Islamic Azad University, Sari, Iran Seyd Abdollah Hashemvarzi 100319475328460018367 100319475328460018367 No Department of Sport Physiology, Sari Branch, Islamic Azad University, Sari, Iran