Objective:To investigate the expression of osteoprotegerin(OPG)/receptor activator of nuclear factor-κB (RANK)/RANK ligand(RANKL) axis in stabilization of spontaneously restored sinus rhythm in permanent atrial fibrillation patients after mitral valve (MV) surgery and study its clinical significance. Methods:Clinical data,biopsies of right atrial appendage were collected from 135 atrial fibrillation patients who spontaneously restored sinus rhythm after conventional isolated MV replacement. Comparison was made between patients who had recurrence of atrial fibrillation within 7 days(AF group) vs. patients with persisted sinus rhythm for more than 7 days(SR group). Results:The result of Western blot and immunohistochemistry showed an increased expression of RANK,RANKL and RANKL/OPG ratio in AF group than SR group. The degree of interstitial fibrosis reflected by collagen volume fraction(CVF) was also more severe in AF group than SR group,which was positively correlated with the expressions of RANK and RANKL and RANKL/OPG ratio. Conclusion:These findings suggest that the OPG/RANK/RANKL axis plays important roles in stabilization of restored sinus rhythm after MV surgery by stimulating AF-related atrial remodeling in atrial fibrillation patients,and possibly represents a new target for upstream treatment of atrial fibrillation.