Objective To investigate the effects of the combination of amiodarone and creatine phosphate sodium on morphological changes, malondialdehyde (MDA) contents and superoxide dismuase (SOD) activity of myocardium in rabbits after cardiopulmonary resuscitation (CPR). Methods The model of cardiac arrest was established by suffocation method. Forty healthy rabbits were randomly divided into five groups: group A (sham group), group B (normal saline group), group C (treatment group with amiodarone 5 mg/kg), group D (treatment group with creatine phosphate sodium 100 mg/kg), group E (treatment group with amiodarone 5 mg/kg combined with creatine phosphate sodium 100 mg/kg). All of the rabbits were put to death immediately at 6 h after CPR. The morphological changes in myocardium were observed under optical microscope and electron microscope. Then determined the levels of MDA and the activity of SOD in myocardium by enzyme-linked immunosorbent assay method. Results Results of pathology showed that myocardial injury in group B were more seriously than in group C and group D, and myocardial injury in group C and group D were more seriously than in group E. Observation under electron microscopy showed that the mitochondria in group A were complete and in normal shape, myofilaments arranged regularly, light bands and dark bands of myofilaments could be observed clearly. In group B, a lot of mitochondria were swollen and vacuolization, cristae broken, myofilament arranged irregularly, light bands and dark bands of myofilaments were vague. In group C and group D, a few mitochondria were vacuolization, cristae broken, light bands and dark bands of myofilaments were vague. In group E, mitochondria were complete, few mitochondria in myocardial cells were swollen, cristae broken, light bands and dark bands of myofilaments were clearly visible. Compared with group A (0.98±0.22), the levels of MDA in myocardium were significantly increased in group B, group C and group D (2.45±0.41, 1.65±0.18, 1.71 ±0.17) (P<0.05). Compared with group B, the levels of MDA were significantly lower in group C and group D (P<0.05). Compared with group E (1.21±0.55), the levels of MDA were significantly higher in group C and group D (P<0.05). There were no significant difference in the levels of MDA between group C and group D (P﹥0.05). Compared with group A (21.4±2.1), the activity of SOD in myocardium was significantly decreased in group B, group C, group D and group E (16.2±0.9，17.9±1.0，18.2±0.6，19.8±1.4) (P<0.05). Compared with group B, the activity of SOD was significantly higher in group C and group D (P<0.05). Compared with group E, the activity of SOD was significantly lower in group C and group D (P<0.05). There were no significant difference in the the activity of SOD between group C and group D (P﹥0.05). Conclusions Treatment with amiodarone and creatine phosphate sodium,especially combination these two drugs,can alleviate myocardial injury after CPR in rabbits. Partly reduce lipid peroxidation and peroxidation injury may be the main mechanisms of protective effects of amiodarone combined with creatine phosphate sodium on myocardium.