Reperfusion arrhythmia (RA) is one of the main complications which are also an important cause of sudden cardiac death. The aim of this study was to clarify whether grape seed proanthocyanidins extracts (GSPE) were therapeutic agents against RA. The models of cardiac ischemic reperfusion injury were established in rabbits. GSPE (100 mg/kg, and 250 mg/kg body weight/d, respectively) were administered for 3 wk. The incidence rates of arrhythmias before and after reperfusion of each group were recorded, cardiac infarction area and microstructures of cardiac cells of each rabbit were observed, and the expression of connexin 43 (Cx43) was detected by immunohistochemistry. Data were analyzed using the Leica Qwin V3 image analysis system. Reperfusion induced arrhythmia. Ventricular fibrillation (VF) occurred during the early phase of reperfusion after ischemia. Our results showed that GSPE treatment significantly reduced the incidence of VF and the infarction size compared with the model control group. Moreover, the intercalated disks in the model control group showed collapse, displacement and even the formation of cisterns. After being treated by GSPE, the intercalated disks were improved and there were less collapse and displacement. The expression of Cx43 was improved by GSPE treatment, and high dose of GSPE resulted in significant improvement. The study suggests that GSPE has a protective effect on myocardial ischemic reperfusion arrhythmias, which may be mediated by inhibiting the degradation of Cx43 and enhancing gap junctional conductance.