Objective To investigate the effects of recombinant human brain natriuretic peptide (rhBNP) on sodium current (INa) in left ventricular myocytes of rabbit heart undergoing ischemia/reperfusion(I/R), so as to explore the cellular (ionic) basis of rhBNP treatment for antiarrhythmia. Methods Forty-five rabbits were randomly divided into three groups (n＝15): ischemic/reperfusion (I/R) group, rhBNP intervention (rhBNP) group and sham-operation control (CON) group. Anesthetized rabbits were subjected to 30min ischemia by ligation of the left anterior descending coronary artery and 120min reperfusion. rhBNP group was injected with rhBNP at a dose of 0.06μg/(kg·min) via ear-vein. Single ventricular myocytes were isolated enzymatically from the epicardial zone of the infracted region derived from the hearts in I/R, rhBNP groups and the same anatomy region in CON group. Whole cell patch clamp technique was used to record INa. Results The peak INa density (at –30mV) was significantly decreased in I/R group [(–22.46±5.32)pA/pF, n＝12] compared with CON group [(–42.78±5.48)pA/pF, n＝16; P＜0.01], while it was significantly increased in rhBNP group[(-37.82±5.45)pA/pF, n＝15] compared with I/R group(P＜0.01). Conclusion Ischemia/reperfusion induces significant down-regulation of INa, and pretreatment with rhBNP could attenuate these changes, prevent and reverse this electrical remodeling.