Abstract: AIM: To observe the effects of cyclosporine-A (CsA) on the expression and distribution of atrial gap-junction protein Cx40/Cx43 in a canine model with atrial fibrillation (AF)-induced atrial tachypacing and to evaluate the inhibition of CsA on AF-induced atrial remodeling. METHODS: Eighteen healthy adult mongrel dogs (weighing 17-23.2 kg and ranging in age from 2 to 4 years) were divided into three groups: 1)sham group no pacemaker was implanted and no interventions; 2)atrial tachypacing (ATP) group high-speed pacemaker was implanted and after 72 h postoperative recovery, the pacemaker was set to work at a rate of 400 bpm for 8 weeks; 3)CsA group all procedures were the same as ATP group, but each canine was given CSA at a daily oral dose of 10 mg/kg. After 8 weeks, all canines were put to death and tissue samples were taken from the atrial free-wall. Expression and distribution of connexin40/connexin43 were detected with immunohistochemistry and Western blot methods. RESULTS: Compared with that in sham group, the expression of Cx40 protein in canine atrium significantly increased in ATP group (P<0.01) and in CsA group (P<0.05), but the changes in CsA group were much smaller than those in ATP group (P<0.05). Compared with that in sham group, expression of Cx43 decreased in both ATP and CsA groups (P<0.01), but the changes in CsA group were much smaller than those in ATP group (P<0.05). The distribution heterogeneity of Cx40/43 increased with the increase of end-to-end conjunction and the decrease of side-by-side conjunction in both ATP and CsA groups. CONCLUSION: CsA inhibits the remodeling of Cx40/Cx43 and the atrial remodeling induced by atrial tachypacing in a canine model.