The object was to investigate the effects and mechanisms of ginsenoside on atrial fibrillation (AF) in rats with heart failure (HF) after myocardial infarction (MI). 24 HF rats were randomly divided into HF group (CF) and Treatment group which were treated with ginsenoside (Treatment) (n = 12, respectively). Ten sham operation control rats were grouped into sham group (Sham). The Treatment group was treated with ginsenoside (10 mg/kg), and the other groups were administrated with the normal saline. After four weeks intervention, echocardiography, AF vulnerability, atrial fibrosis, connexin 43, PI3K, AKT, Nrf2 protein expression were assessed. Ginsenoside resulted in an attenuation of arrhythmogenic left atrial remodeling, with a significant reduction in left atrial diameter (P < 0.01), AF inducibility and duration, and atrial fibrosis (P < 0.05), and an increase of protein expression of Cx43 and up-regulation of PI3k/Akt/Nrf2 signaling pathway (P < 0.05). Ginsenoside has the potential to reduce arrhythmogenic atrial remodeling and AF vulnerability via anit-fibrosis, inhibiting gap junction remodeling by up-regulating PI3K/AKT/Nrf2 signaling pathway.