Background; Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, induce electrical remodeling. Electrical remodeling can to be related to tachycardia-induced modification of caveolae, a subset of membrane lipid rafts. The structural caveolar protein, caveolin-3 interacts with NADPH oxidase and endothelial nitric oxide synthase (eNOS) in atrial myocytes. We investigated the effects of caveolar disruption agent, methyl-beta-cyclodextrin (M棺CD) and statins in modification of caveolin-3 in the cross talk between reactive oxygen species (ROS) and nitric oxide (NO) signaling by tachypacing. Methods and Results; Mouse atrial myocyte (HL-1 cell) were cultured in the presence of rapid pacing for 24h. Tachycardia-induced alteration were evaluated from stimulated cells, as well as intact cells cultured with M棺CD (3 mM), simvastatin (10 關M) or pravastatins (10 關M). The expression of the caveolin-3 was significantly increased by tachypacing (160짹19 % of control, p<0.05), treatment with M棺CD suppressed to control levels. Pacing of atrial myocyte increased the intracellular ROS generation to 180짹12 % of control, which was significantly attenuated by M棺CD and statins (p<0.05). In addition, expression of NADPH oxidase subunit gp91phox (NOX2) and p47phox were also increased in pacing-stimulated atrial myocyte, whereas inhibited by M棺CD. Rapid stimulation of atrial myocyte for 24 h markedly increased NO production (1.39짹0.06 關M, p<0.05). Phosphoylation of eNOS (ser1177) also significantly increased by pacing to 185짹30.4 % of intact atrial myocyte, while it was not modified by all treatments (p<0.05). Conclusion; In HL-1 cell, caveolin expression was increased after rapid pacing. M棺CD effectively inhibits pacing induced expression of caveolin-3 expression and ROS/NO signaling in pacing-stimulated mouse atrial myocyte.