Electroacupuncture (EA) therapy has widely been accepted as a useful therapeutic technique with low risk in the clinical setting for prevention from cardiac disease. However, the physiological mechanism under which this protective effect works remains unclear. The present study investigated the effects of EA pretreatment on myocardial ischaemia/reperfusion (MI/R) injury in mice and its possible signalling pathway. Mice were randomly divided into Sham, MI/R, EA + MI/R, EA(–) + MI/R, and AM630 + EA + MI/R groups. We reported that EA pretreatment significantly ameliorated MI/R injury, evidenced by increased cardiac function, reduced infarct size, and decreased apoptosis. This was associated with a reduction of oxidative stress in the infarcted myocardium, which was through CB2. The CB2 expression was up-regulated in the heart after EA pretreatment, as well as heart tissue content of N -arach-idonoylethanolamine-anandamide and 2-arachidonylglycerol. Furthermore, the expression of adenosine...