Abstract: AIM:To explore the effects of rapamycin (RAPA) on atrial fibrosis in rats treated with high isoproterenol (ISO). METHODS: Twenty-seven male Wistar rats were randomly divided into control group, ISO group ［5 mg/(kg·day) for 7 days］ and ISO+RAP group ［3 mg/(kg·day) for 2 weeks］. Mice were sacrificed after 15 days. Angiotensin II (AngII) content in myocardial tissue was measured by radioimmunoassay, HIF-1α and TGF-β1 were detected by immunohistochemistry and Western blot, and atrial fibrosis was determined on H-E and Masson stained heart sections. RESULTS: Compared with the control group, AngII content increased in ISO group and ISO+RAP group (P<0.01). The degree of atrial fibrosis in ISO+RAP group was significantly lower than that in ISO group (P<0.01) and no atrial fibrosis was seen in control group. HIF-1α and TGF-β1 expressions of myocardium increased in ISO group compared with those in control group (P<0.01) and decreased in ISO+RAP group compared with those in ISO group (P<0.01). CONCLUSION: HIF-1α may be involved in atrial fibrosis and RAPA can efficiently improve atrial fibrosis by repressing the expressions of HIF-1α and TGF-β1.