Abstract Background Levosimendan exerted favorable effects on the initial outcome in the treatment of ventricular fibrillation cardiac arrest. This study investigated the efficacy of levosimendan in the treatment of asphyxia-induced cardiac arrest in rats. Methods Animals underwent asphyxial cardiac arrest/cardiopulmonary resuscitation, randomized to three treatment groups: epinephrine (10 μg/kg) supplemented with levosimendan (bolus 12 μg/kg and infusion for 1 h, EL group); epinephrine only (10 μg/kg, E group), or levosimendan only (bolus 12 μg/kg and infusion for 1 h, L group). The resuscitation success rate, wet-to-dry ratio of lung, and rate of alveolar and blood gas analysis were recorded. Results 10 rats in the EL group, 8 in the E group, and 2 in the L group showed an initial return of spontaneous circulation ( P