Background: Endothelin is elevated in heart failure (HF) and contributes to neurohormonal activation, hemodynamic deterioration, and cardiovascular remodeling. But relation to atrial fibrillation (AF) was not much studied. Also LIFE study reported decreased AF incidence after losartan treatment. Here, we studied relation of endothelin in AF development and AF prevention mechanism of losartan by endothelin system. Methods: A rat myocardial infarction (MI) model was used. Two days after induction of MI, rats were randomized into 3 groups: the sham group, the MI group, and the MI+Losar group (losartan 10mg/kg/day for 10 weeks). Echocardiography, AF induction, and atrial fibrous tissue content analysis were done. Western blotting of endothelin receptor A (ETa) and B (ETb) were done. Results: Ejection fractions were significantly decreased in MI group. Fibrosis quantification showed significantly increased left atrial fibrosis in MI and significantly attenuated in MI+Losar group. Duration of AF were increased in MI group and significantly decreased in MI+Losar group. Left atrial tissue western blotting showed, ETa was increased significantly and ETb was significantly decreased in MI group but these were significantly attenuated in MI+Losar group. Conclusion: Alternation of endothelin system was associated with increased AF duration. These changes were attenuated after losartan treatment. This finding was novel AF prevention mechanism for losartan in HF