Objective To investigate the association of epicardial adipose tissue thickness（EATT） measured by echocardiography and the circulating levels of inflammatory factors with atrial fibrillation（AF）. Methods A total of 89 patients with AF who were treated in Department of Cardiology，The First Affiliated Hospital of Chongqing Medical University，were enrolled as observation group，and 21 patients with sinus rhythm were enrolled as control group. All patients underwent echocardiography to measure EATT of the free wall of the right ventricle，and related data were collected，including general information，biochemical parameters，ultrasound measurements，and complications. Based on the exclusion criteria，there were finally 50 patients with AF and 20 controls. Peripheral serum was collected from these patients，and ELISA was used to measure the serum levels of inflammatory factors. The association of EATT and inflammatory factors with AF was analyzed. Results The association between EATT and AF was analyzed among 89 patients with AF and 21 controls，and the results showed that compared with the control group，the AF group had significantly higher age，blood urea nitrogen，serum creatinine（Scr），left atrial diameter（LAD），and EATT and significantly lower total cholesterol，low-density lipoprotein cholesterol，and left ventricular ejection fraction. The binary multivariate logistic regression analysis showed that age，Scr，LAD，and EATT were independent risk factors for AF. The association of EATT and inflammatory factors with AF was analyzed among 50 patients with AF and 20 controls，and the results showed that the AF group had significantly higher EATT and circulating levels of interleukin-8（IL-8） and interleukin-10（IL-10） than the control group. The receiver operating characteristic（ROC） curve analysis showed that EATT，IL-8，and IL-10 had an area under the ROC curve（AUC） of 0.746，0.769，and 0.721，respectively，in predicting AF，while the combination of EATT，IL-8，and IL-10 had an AUC of 0.826（95%CI=0.720-0.932，P=0.000） in predicting AF，with a sensitivity of 68% and a specificity of 90%. The patients were divided into groups based on the cut-off value of 18.7 pg/mL for IL-8，and there was no significant difference in EATT between groups；the patients were divided into groups based on the cut-off value of 5.886 pg/mL for IL-10，and the results showed that the IL-10≥5.886 pg/mL group tended to have a larger EATT（P=0.022）. The Spearman correlation analysis showed that EATT was positively correlated with tumor necrosis factor-α（TNF-α） in the AF group（r=0.422，P=0.002）. Conclusion The increase in EATT is closely associated with AF，and EATT is an independent risk factor for AF. There are significant increases in the circulating levels of IL-8 and IL-10 in patients with AF. EATT combined with IL-8 and IL-10 has a higher value in predicting AF and may help with the early identification，diagnosis，and treatment of AF. There is a significant increase in EATT in the high IL-10 subgroup，and EATT is positively correlated with TNF-α in the AF group，suggesting that EATT may be involved in the development and progression of AF through inflammatory effects.