Cardiac Contractility Modulation (CCM) is a novel device-based therapy for chronic heart failure. This study aimed to explore the effects of CCM on electrophysiological characteristics of heart failure. Rabbits were randomly divided into sham group (n=10), HF group (n=10) and CCM group (n=10). The rabbit chronic heart failure model was induced after 12 weeks aortic constriction. Then CCM was delivered to the anterior wall of left ventricle lasting six hours per day for 4 weeks. Changes in cardiac function and electrophysiological characteristics were monitored and SERCA2a expression was detected by quantitative real time qRT-PCR and Western blot analysis. Compared to sham group, HF group showed decreases in LVEF, LVFS, E/A ratio, VFT and increase in QTc and ERP, as well as decreased mRNA and protein levels of SERCA2a (P<0.05). CCM restored LVEF, LVFS, E/A ratio, LVESD, LVEDD, VFT, QTc and ERP, and SERCA2a expression levels in rabbits with heart failure to sham group. In conclusion, CCM benefits cardiac function and electrophysiological characteristics in rabbit model of chronic heart failure, perhaps due to the up regulation of SERCA2a expression.