Non-pharmacological in vivo models of atrial fibrillation (AF) have been developed in large animals only. We aimed to develop and characterize a new small animal non-pharmacological in vivo model of AF. AF was induced by transesophageal atrial burst pacing during 35 seconds periods of asphyxia in anesthetized male Sprague-Dawley rats. AF was reproducibly induced in 81% of the rats. The presence of AF was associated with an increased heart rate, and a decreased blood pressure. Treatment with amiodarone, D,L-sotalol, flecainide, and propranolol all reduced duration of AF, whereas verapamil treatment was associated with a marked profibrillatory effect. Increasing gap junction intracellular communication using the antiarrhythmic peptide analogue AAP10 did not affect AF duration. Basal plasma level of epinephrine and norepinephrine were increased 5- to 20-fold relative to values reported by others, but unchanged following 35 seconds of asphyxia. The results from our study demonstrate that the rat model shares several clinical key characteristics with human AF: (1) hemodynamic response to AF; (2) increased autonomic tone; (3) antiarrhythmic effects of clinically used drugs; (4) profibrillatory effect of verapamil. Relative to existing models of AF in larger animals, this model offers rapid, predictive, and inexpensive testing of antiarrhythmic/profibrillatory effects of new drugs.