Our aim was to examine the effects of aqueous extracts of fermented (CFE) and non-fermented (CNFE) ¨copoazú¨ (fruit of Theobroma grandiflorum) seeds against ischemia-reperfusion injury. Isolated rat hearts were submitted to 30 min of global ischemia (GI) and 60 min of reperfusion (R). Other hearts received CFE or CNFE in absence or in presence of L-NAME (a nitric oxide synthase inhibitor). Infarct size (IS) and postischemic myocardial function (PMF) were measured. Lipid peroxidation, reduced glutathione (GSH) and the expression of phosphorylated forms of eNOS, Akt, GSK-3b and PKCe were assessed. The response of isolated mitochondria to Ca2+ (MR) was also determined. CFE but not CNFE decreased IS, increased PMF and the expression of P-eNOS, P-Akt, P-GSK-3b and P-PKCe, partially preserved GSH and improved MR. These effects were lost in presence of L-NAME. These data demonstrate that the acute treatment with CFE protects the heart against ischemiareperfusion damage through NOS-dependent mechanisms.