Trichinella spiralis infects striated muscle cells and causes one of the most important parasitic diseases. The rapidly growing intramuscular larvae depend on insulin signaling pathways to supply their needs of glucose and glycogen. Irisin is a myokine secreted by skeletal muscles during exercise to increase energy expenditure by stimulating glucose uptake and accumulation of glycogen in muscle cells. This study investigated the potential role of irisin during experimental trichinosis. Thirty albino mice were infected orally with T. spiralis (200larva/mouse) and five healthy mice were assigned as normal control. On the 7 th , 14 th , 21 st , 28 th , 35 th , &48 th day postinfection, mice were evaluated regarding the changes in body weight, blood glucose level, serum insulin, histopathological changes, glycogen storage, and immunohistochemical expression of irisin. The results revealed that during the early stage, from the 7 th to 28 th dpi there were gradual insignificant decreases in mice body weight. Blood glucose levels showed significant decreases and the lowest was on the 21 st and 28 th dpi (83.6±3.05 and 95.6±5.08, respectively). Also, during this phase, there were significant increases in serum insulin and the highest was on the 21 st dpi (8.7±0.34). These changes correlated with the development and growth of nurse cells parallel with increased glycogen accumulation and irisin expression in muscle bundles. During the late stage, there were significant decreases in body weight, significant increases in blood glucose levels, and significant decreases in serum insulin. The histopathological examination revealed intense cellular inflammatory infiltrate associated with glycogen depletion. Strong irisin expressions were observed in the inflammatory infiltrates, nerve bundles, and the adjacent adipose tissues while in muscle bundles it decreased. In conclusion, the increased irisin expression in muscle bundles is suggested to increase insulin secretion and responsiveness of T. spiralis-infected muscles to facilitate glucose transport and glycogen accumulation during larval growth. Whereas, during the late stage, irisin affects fat metabolism and might contribute to loss of body weight. The increased irisin expression in the inflammatory infiltrates may have protective and anti-inflammatory roles. However, further studies should be conducted to discover in-depth role of irisin and host-endocrine interplay during T. spiralis infection.