Obstructive sleep apnea is characterized by intermittent obstruction of upper airway which leads to intermittent hypoxia. Myocardial glycogen is a major energy resource for heart during hypoxia. Previous studies have demonstrated that intermittent hypoxia rapidly degrades myocardial glycogen and activates glycogen synthase (GS). However, the underlying mechanisms remain undefined. As sleep apnea/intermittent hypoxia usually happen at night, whether intermittent hypoxia leads to GS activation in the post-absorptive state is not known. In the current study, male adult rats were studied after either an overnight fast or ad lib feeding with or without intermittent ventilatory arrest. Hearts were quickly excised and freeze-clamped. Intermittent hypoxia decreased myocardial glycogen content in fed rats and stimulated GS in both fasted and fed rats. However, the portion of GS in the active form increased by ~ 38% in fasted rats, compared with a larger ~130% increase in fed rats. The basal G-6-P content was comparable in fasted and fed animals and increased ~ 3-fold after hypoxia. The basal phosphorylation states of Akt and GSK-3 and the activity of protein phosphatase 1 (PP1) were comparable between fasted and fed control rats. Hypoxia significantly increased Akt phosphorylation and PP1 activity only in fed rats. In contrast, hypoxia did not induce significant change in GSK-3 phosphorylation in either fasted or fed rats. We conclude that hypoxia activates GS in fed rat myocardium through a combination of rapid glycogenolysis, elevated local G-6-P content and increased PP1 activity and fasting attenuates this action independent of local G-6-P content.