Objective: To clarify adenosine triphosphate sensitive potassium (KATP ) channels' role in glucocorticoid induced myopathy induction. Materials and methods: 48 adult male rats divided into two experiments. Experiment Ⅰ: 32 rats divided equally into four group; Group Ⅰ: control group, Group Ⅱ: (Dexa group) (Dexamethasone 500 μg/kg once daily i.p), Group ΙΙΙ (Dexa+ Nicorandil) (Nicorandil (3 mg/kg) per oral once daily), Group ΙV (Dexa+Glibenclamide) (Glibenclamide (10 mg/kg) per oral once daily) all for 10 days. By the end of the experiment, blood samples were collected for blood glucose, serum insulin, potassium and creatine kinase-MM. Tibialis anterior muscles were isolated for contractility recording, oxidative stress measurement, histopathological examination and immunohistochemistry for insulin like growth factor-1(IGF-1). Experiment Ⅱ:16 rats (8 normal and 8 glucocorticoid induced myopathy rats). From each rat, the tibialis anterior was isolated and incubated with nicorandil (100 μmol /L for 10 minutes) and glibenclamide (1μmol /L for 5 minutes) for contractility recording. Results: Contractile properties, histopathological changes and IGF-1 muscle expression are improved with glibenclamide (KATP channel blocker) and worsened with nicorandil (KATP channel opener). CK-MM level significantly increased with nicorandil, while normal with glibenclamide. Serum potassium and blood glucose significantly increased with nicorandil and decreased with glibenclamide. Serum insulin significantly decreased with nicorandil and increased with glibenclamide. The oxidative stress state insignificantly changed with both drugs (p value ≤0.05 was considered to be statistically significant). Conclusion: Opening of KATP channels seems to have a role in the induction of glucocorticoid-induced myopathy probably by decreasing IGF-1 expression.