Animal models of cardiac arrhythmia are important tools for analyses of antiarrhythmic drug mechanisms and medical laboratory teaching. In this study, two major models, namely, barium chloride-induced arrhythmia in rabbits and ouabain-induced arrhythmia in guinea pigs, were systematically compared in terms of technical principles, modeling method, and indexes. By optimizing electrocardiographic parameters, standardizing arrhythmia grading criteria, and introducing quantitative analysis method, we revealed differences between the two models in terms of ion channel mechanisms, drug targets, and applicability to teaching. The barium chloride model was characterized by rapidly induced ventricular arrhythmia, which is suitable for the observation of acute drug efficacy. The ouabain model simulated the development of progressive arrhythmia, which is suitable for the study of the preventive effects of anti-arrhythmic drugs. This study provides a technical reference for the selection of arrhythmia models, optimization process, and mechanistic analyses in medical experimental teaching and is of great significance for improving the electrophysiology experimental skills of medical students.