It has been recently reported that atrial fibrillation (AF) is associated with inflammation and inflammatory cytokines, and n-3 polyunsaturated fatty acids (PUFAs) might be of anti-inflammatory effects. This study was to evaluate the anti-inflammatory effect of PUFAs on AF in a canine sterile pericarditis model. 20 dogs were randomly assigned to two groups: control group (10 dogs) and PUFA treatment group (10 dogs), in which sterile pericarditis was created by open-chest operation. PUFAs were administered orally (2g/day) 4 weeks before the operation till the end of the study. Before and 2 days after the operation, CRP, IL-6, TNF-α levels, the inducibility and maintenance of AF, the atrial effective refractory period (AERPs), and intra-atrial conduction time were determined. Before the operation, there were no significant differences in any of the parameters between the two groups. On the second postoperative day, the PUFA group had a lower CRP level (7.6 ± 0.5 vs. 11.7 ± 1.3mg/dl, P<0.0001), a lower IL-6 level (112.0 ± 37.3 vs. 142.0 ± 19.6 pg/ml, P<0.01), a lower TNF-α level (83.3 ± 8.5 vs. 112.4 ± 8.2 pg/ml, P<0.0001), a less AF inducibility (percentage of burst attempts leading to AF episodes: 11 ± 7.4 vs. 28 ± 10.3, P<0.001) and maintenance [median AF duration: 1105 s (655.8-1406.5) vs. 2516.5 s (1187-3361), P<0.05], a longer AERP (133.4 ± 4.1 vs. 129.8 ± 4.3 ms, P<0.05), and a shorter intra-atrial conduction time (46.6 ± 4.4 vs. 51.9 ± 4.8 ms, P<0.05) than the control group. Dietary n-3 PUFA supplementation attenuates the inducibility and maintenance of AF in the sterile pericarditis model by reducing the production of proinflammatory cytokines. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.