To observe the effects of Shenmai injection on post-cardiac arrest syndrome (PCAS) in rabbit and to discuss the underlying mechanism. Seventy-three rabbits were divided into sham operation group (n=10), model group (n=21), high and low dosage Shenmai group (each n=21) by random number table method. The animal model of cardiac arrest was reproduced by clamping the endotracheal tube. The rabbits in sham operation group were only given anesthesia and tracheostomy without producing asphyxia by clamping the trachea to produce asphyxia. Serum creatine kinase isoenzyme (CK-MB), alanine aminotransferase (ALT), creatinine (Cr), troponin I (cTnI), tumor necrosis factor-α (TNF-α), interleukin (IL-1β, IL-6) and nuclear transcription factors-ΚB (NF-ΚB) levels were determined before asphyxia and 3, 6, 12, 24, 48 hours after restoration of spontaneous circulation (ROSC), and dynamic changes in various parameters were determined in each group. All the indexes in model group and Shenmai groups were gradually increased after ROSC. IL-6 peaked at 6 hours, IL-1β peaked at 12 hours, CK-MB, cTnI, TNF-α and NF-ΚB peaked at 24 hours, ALT and Cr peaked at 48 hours. CK-MB, ALT, cTnI levels in high dosage Shenmai group were significantly lower than those in the model group 6 hours after ROSC [CK-MB (U/L): 571.69±24.39 vs. 587.98±22.38, ALT (U/L): 74.88±8.71 vs. 81.49±5.79, cTnI (μg/L): 7.82±1.52 vs. 8.97±1.87], serum levels of TNF-α and NF-ΚB 12 hours after ROSC [TNF-α(ng/L): 120.36±12.38 vs. 135.23±20.13, NF-ΚB (ng/L): 2.18±0.17 vs. 2.29±0.15], and the serum levels of IL-1β and IL-6 24 hours after ROSC in high dose Shenmai group were significantly lower than those in the model group [IL-1β (ng/L): 1.49±0.13 vs. 1.62±0.17, IL-6 (ng/L): 72.01±5.02 vs. 79.35±11.28], however, serum Cr in high dosage Shenmai group was significantly lower than in the model group at 24 hours after ROSC (μmol/L: 158.73±4.40 vs. 162.97±5.02, P<0.05 or P<0.01). In low dosage Shenmai group, the serum level of CK-MB, Cr, cTnI were significantly lower than those in the model group 24 hours after ROSC [CK-MB (U/L): 1 769.00±19.73 vs. 2 120.96±24.15, Cr (μmol/L): 159.32±3.02 vs. 162.97±5.02, cTnI (μg/L): 12.17±3.04 vs. 14.89±3.09,P<0.05 or P<0.01). But after ROSC, ALT, TNF-α, IL-1β, IL-6 and NF-ΚB showed no significant change as compared with model group. In high dosage Shenmai group, serum levels of CK-MB and cTnI at 6, 12 hours and TNF-α and IL-6 at 24 hours after ROSC were significantly lower than those in the low dosage Shenmai group(all P<0.05). Severity of injury of different organs in rabbit cardiac arrest model showed positive correlation with the alterations in serum TNF-α, IL-1β, IL-6, NF-ΚB after cardiopulmonary resuscitation. Early use of Shenmai injection after cardiopulmonary resuscitation can retard the development of PCAS, especially in the protection of ischemia and hypoxia of myocardium after cardiopulmonary resuscitation.