Background: Recent reports have noted the favorable pleiotropic effects of sildenafil on the heart failure.We tested the hypothesis that chronic treatment with sildenafil attenuates left ventricular (LV) remodeling and prevents exercise intolerance in chronic MR. Method: MR was created in Sprague Dawley rats by making a hole with a 23 gauge needle on mitral leaflet through LV apex. After MR and LV dilatation were confirmed by echocardiography 2 weeks after the operation, rats were randomly assigned to sildenafil treatment (MR+SIL, 100mg/kg p.o. qd, N=15) or vehicle only group (MR+VEC, N=15) and continued for 4 months. Twelve sham rats were compared to MR rats. Results: Two of 15 rats in VEC groups died during the study period. No death were noted in SIL and sham group. After 4 month, LV dilatation was less severe in SIL compared to VEC (LV end-systolic dimension, 4.7짹0.3 for sham vs 5.9짹0.3 for SIL vs 7.4 짹 0.5 mm for VEC, p<0.05; LV end-diastolic dimension,8.3짹0.4 vs 10.5짹0.2 vs 11.7짹0.61 mm, p<0.05). LV ejection fration was greater in SIL than VEC(70.2%짹2.2 for sham vs 67.0짹4.2 for SIL vs 58.9짹2.5, p=0.01). In pressure-volume analysis, SIL showed greater LV end-systolic pressure-volume relation than VEC. Serial treadmill test revealed that exercise capacity was reduced in VEC but not in SIL (exercise duration, 767 짹127 sec for sham vs 705짹140 SIL treated MR vs 390짹170, p = 0.01). In microarray analysis, there were significant changes in expression of genes linked to apoptosis, inflammation, ROS, DNA damage related gene however not MMP families or fibrosis. Pathological analysis showed no significance difference of perivascular and interstitial fibrosis in three groups whereas the percentage of TUNEL-positive cells was two fold greater in VEC versus sham and SIL. Conclusion: Sildenafil significantly attenuates LV remodeling and prevents exercise intolerance in a rat model of chronic MR. This benefit might be associated with anti-apoptotic, anti-oxidative, anti-inflammatory effects of sildenafil.