Irisin plays an important role in energy metabolism and regulation of metabolic diseases as obesity and diabetes. This study aimed to evaluate the modulatory effect of physical exercise on the irisin as an exercise stimulated hormone and other biochemical parameters in obese rats suffering from metabolic syndrome (MS). Sixty male albino rats were randomly divided into 4 groups (15 in each): group I (control) healthy rats were fed on standard (St.) diet, group II (contol+ex) in which rats were fed on St. diet and made exercise (ex.), group III: rats were fed on high carbohydrate high fat (HCHF) diet induced obesity in rats. Group IV (HCHF+ex.): rats also fed on HCHF diet and made exercise for 20 weeks. Serum glucose, insulin, lipid profile, irisin, Peroxisome proliferator-activated receptor -alpha (PPAR-𝛼) and Interleukin 6 (IL-6) were measured. Histopathological examination of liver, pancreas and muscle was done. Our results revealed that glucose, lipid profile except HDL-C and IL-6 significantly increased, whereas a remarkable decrease in serum level of irisin and PPAR-α in HCHF group comparing to the control group. After swimming, all parameters were improved. Conclusion: swimming exercise has an efficient effect in improving all biochemical parameters of MS due to releasing of irisin which has regulatory mechanisms with respect to metabolic metabolism -associated health issues.