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Aim: Cardiac arrhythmias are among the most important pathologies that cause sudden death. The exploration of new therapeutic options against arrhythmias with low undesirable effects is of paramount importance. Methods: However, the convenient and typical animal model for screening the potential lead compound becomes a very critical modality, particularly in anti-arrhythmia. In this study, mice were intraperitoneally (i.p.) injected with BaCl₂, CaCl₂, and adrenaline to induce arrhythmia, and simultaneously compared with BaCl₂-induced rats. Results: Electrocardiogram (ECG) showed that the majority of mice repeatedly developed ventricular bigeminy, ventricular tachycardia (VT), and ventricular fibrillation (VF) after BaCl₂-injection as seen in rats. The ECG of mice developed ventricular bigeminy and VT after CaCl₂ and AT after adrenaline i.p. injection. Additionally, acute cardiac arrhythmia after BaCl₂ i.p. injection could be reverted by drugs (lidocaine and amiodarone) administration. Additionally, the different routes of administration for various chemical-induced arrhythmia in both mice and rats were also retrieved from PubMed and summarized. Comparing this approach with previous studies after the literature review reveals that arrhythmia of BaCl₂-induced i.p. mice is compatible with the induction of other routes. Conclusions: This study brings an alternative experimental model to investigate antiarrhythmic theories and provides a promising approach to discovering new interventions for acute arrhythmias.