To investigate the effect of Huatan Quyu Formula on the serum matrix metalloproteinase-2(MMP-2) and tissue inhibitor of metalloprotease-2(TIMP-2) levels in rats with atrial fibrillation and explore the mechanism of Huatan Quyu Formula for preventing and treating atrial fibrillation.Methods:Sixty male Sprague-Dawley(SD) rats were randomly divided into a control group，a model group，high-，medium-，and low-dose Huatan Quyu Formula group，and a verapamil group.The atrial fibrillation model was induced by tail vein injection of acetylcholine chloride(ACh，66 μg/mL)-CaCl2(10 mg/mL) for seven days.After two weeks，the duration of atrial fibrillation was monitored using limb lead Ⅱ ECG recorded by the PowerLab 15T data acquisition and analysis system.The serum MMP-2 and TIMP-2 levels were measured by enzyme-linked immunosorbent assay(ELISA).Results:Duration of atrial fibrillation.The duration of atrial fibrillation in the model group was significantly prolonged compared with that in the control group(P<0.05).The duration of atrial fibrillation was significantly shorter in the groups with drug intervention than that in the model group(P<0.05).Serum MMP-2 and TIMP-2 levels.The serum MMP-2 level increased(P<0.05) and the TIMP-2 level decreased(P<0.01) in the model group compared with that in the control group.The serum MMP-2 level decreased(P<0.05) and the TIMP-2 level increased(P<0.05) in the verapamil group，high-and medium-dose Huatan Quyu Formula groups compared with that in the model group.Conclusion:The Huatan Quyu Formula can shorten the duration of atrial fibrillation in ACh-induced rats，change the ultrastructure of rat myocardium，reduce the serum MMP-2 level，increase the TIMP-2 level，and inhibit myocardial fibrosis caused by atrial fibrillation.These results provide a scientific theoretical basis for the treatment of atrial fibrillation with the Huatan Quyu Formula.