Transgenic (R120G TG) mice with overexpression of an arg120gly missense mutation in HSPB5 display desmin‐related cardiomyopathy. Recently, the cardioprotective effect of nicorandil has been shown to prolong survival in R120G TG mice. However, whether the TG mice exhibit ventricular arrhythmias and nicorandil can inhibit these arrhythmias remains unknown. We examined the effects of chronic administration of nicorandil on ventricular electrical remodeling and arrhythmias in R120G TG mice. Nicorandil (15mg/kg/day) or vehicle was orally administered in R120G TG mice from 5 weeks to 30 weeks of age. Electrocardiogram (ECG) and optical action potentials were recorded from R120G TG mouse hearts. We examined the expression of ventricular connexin43 and cardiac Na+ channel (Nav1.5) in the TG mice. All ECG parameters tested were prolonged in R120G TG mice. Nicorandil improved the prolonged P, PQ, and QRS complex intervals in R120G TG mice. Interestingly, impulse conduction slowing and increases in the expression of total and phosphorylatedconnexin43 and Nav1.5 were observed in R120G TG ventricles. Nicorandil improved ventricular impulse conduction slowing and normalized the increased protein expression levels of total and phosphorylated connexin43,but not of Nav1.5,in R120G TG mouse hearts. The electrical rapid pacing at the ventricle induced ventricular tachyarrhythmias (VT) in 6 of 8 R120G TG mouse hearts but in none of 8 nicorandil‐treated R120G TG mouse hearts (p<0.05). These findings demonstrated that nicorandil inhibitedcardiac electrical remodeling and theprevention of VT by nicorandil was associated with the normalization of connexin43 expression in this model. This article is protected by copyright. All rights reserved.