<h3>Objective</h3> To investigate the role of ILK in ventricular arrhythmia after ischemia-reperfusion (I/R) in isolated hearts. <h3>Methods</h3> Langendoff perfused rat hearts were subjected to 30 min of regional ischemia which induced by deligating the left anterior descending coronary artery, then 30 min of reperfusion. After pretreatment with regulator of ILK activity, Surface ECG was used to observe arrhythmia continuously,and the expression and distribution of connexin 43 were detected via western blot and immunofluorescence. <h3>Results</h3> 1. The agonist of ILK could attenuate ventricular arrhythmia after I/R. As compared with I/R group, the agonist could reduce the ventricular arrhythmia score and the incidence of ventricular arrhymia after reperfusion (p < 0.05), in contrast, the ILK inhibitor Cpd22 could increase the ventricular arrhythmia score and the incidence of ventricular arrhymia after reperfusion (p < 0.05) ,and abolish the anti-arrhythmic effect of ILK agonist. 2. There were no significant differences in Cx43 expression among all groups. ILK agonist could inhibit the remoldeling of Cx43 and reduce the lateralization, contrastly, Cpd22 could promote the lateralization of Cx43. <h3>Conclusion</h3> ILK can imprve reperfusion ventricular arrhythmias by inhibiting remodelling of Cx43, and regulating ILK activity may be a potential therapeutic for reperfusion ventricular arrhythmias.