Abstract: OBJECTIVE To evaluate the potential therapeutic effects and mechanism of shikonin on atrial fibrillation in vivo. METHODS Male Sprague-Dawley rats were injected with Ach-CaCl₂ mixture to make atrial fibrillation model. They were divided into blank group， model group and shikonin group. 4 mg/(kg·d) Shikonin was given to the shikonin group by one-week gavage in advance， Then given Ach-CaCl₂ mixture at the same time. The effects of shikonin on atrial fibrillation in rats were evaluated by electrocardiogram， color Doppler ultrasound， Masson staining， ELISA and Western blot. RESULTS Electrocardiogram showed that shikonin prolonged the induction time of atrial fibrillation; color ultrasonographic results showed that shikonin improved heart enlargement in rats with atrial fibrillation; shikonin inhibited serum inflammatory factors IL-6 and TNF-α in rats with atrial fibrillation; Western blot also showed that shikonin inhibited the expression of IL-6 and TNF-α in atrial tissue of atrial fibrillation rats. CONCLUSION Shikonin shows a protective effect on a rat model of atrial fibrillation.