Background: Thyroid dysfunction is one of the most common metabolic disorders that has not been dependent yet in its diagnosis on evaluation of serum levels of thyroid stimulating hormone (TSH), tri-iodothyronine (T3), thyroxine (T4). Other  markers like serum irisin which is an adipo-myokine secreted by muscles during exercise, and serum creatine kinase (CK) which is a marker of muscle damage, show changes in their levels with hypo and hyperthyroidism in different species. Objective: To evaluate the levels of both serum irisin and serum creatine kinase in hypo- and hyperthyroid rats, and to illustrate the relationship between their levels and thyroid function tests.  Methods: This study was performed on 30 adult healthy male local strain albino rats that were divided into three equal groups: Group I (Control " Euthyroid" group): Fed on commercial rat laboratory chow, Group II (Hypothyroid group): Hypothyroidism was induced by administration of  propylthiouracil, and Group III ( Hyperthyroid group): Hyperthyroidism was induced by administration of T4. BMI in each group was calculated at the end of the experiment. Hormonal assay was performed to measure serum levels of TSH, FT3, FT4, insulin, glucose, irisin and CK. Results: Serum irisin was negatively correlated with TSH levels, and positively correlated with FT3 and FT4 levels in both hypo-and hyperthyroid groups. However, serum CK was positively correlated with TSH levels and negatively correlated with FT3 and FT4 levels in both hypo-and hyperthyroid groups. Also, a negative correlation between serum irisin and serum CK was recorded in both cases of thyroid dysfunction. Conclusions: Serum irisin level decreased in hypothyroid and increased in hyperthyroid rats. At the same time, serum CK level   increased in hypothyroid and decreased in hyperthyroid rats. Both serum irisin and CK levels may be considered as parameters for diagnosis of both hypo-and hyperthyroidism in rats.