Ｏｂｊｅｃｔｉｖｅ　Investigating the effect of ulinastatin on brain injury after asphyxiating cardiac arrest and cardiopulmonary resuscitation (CA/CPR) in rats.　Methods　A total of sixty-three clean male SD rats were randomly allocated into sham operation group (sham group), CA/CPR group (CA group) and ulinastatin administration group (UTI group), 21 rats per group. Rats did not receive CA/CPR in sham group. The model of cardiac arrest induced by asphyxia was established and cardiopulmonary resuscitation was performed in CA group. Ulinastatin with the dose of 105 U/kg was intravenously injected at the onset of resuscitation in UTI group. The same volume of saline was administrated to rats by intravenous injection in sham group and CA group at the same time point. Brain tissue including hippocampus was collected after the experiment. Subsequently, the wet/dry weight ratio (W/D) of brain tissue was determined. The concentration of interleukin (IL)-6 and IL-8 in the hippocampus was tested by enzyme-linked immunosorbent assay (ELISA). The expression of extracellular signal-regulated kinase (ERK)1/2 and protein kinase B (Akt) mRNA in the hippocampus were detected by reverse transcriptive polymerase chain reaction (RT-PCR). The expression of phosphorylate-ERK1/2 (p-ERK1/2) and phosphorylate-Akt (p-Akt) protein in the hippocampus were measured by Western bolt. The morphological changes of brain of rats were observed under light microscopy. The number of normal pyramidal neurons was determined. The ultrastructural changes of brain of rats were observed under light microscopy and the average score of mitochondrial damage was tested.　Results　Compared with sham group, W/D ratio of brain tissue, the average score of mitochondrial damage and the concentration of IL-6 and IL-8, the expression of ERK1/2 and Akt mRNA, p-ERK1/2 and p-Akt protein in the hippocampus were obviously significantly higher(P<0.05), while the number of normal pyramidal neurons was lower in CA group and UTI group (P<0.05). Compared with CA group, W/D of brain tissue, the average score of mitochondrial damage and the concentration of IL-6 and IL-8, the expression of ERK1/2 and Akt mRNA, and p-ERK1/2 and p-Akt protein in the hippocampus were lower (P<0.05), while the number of normal pyramidal neurons was higher in UTI group (P<0.05). Morphology and ultrastructure of rat hippocampus showed no obvious damage in sham group. But significant damage occurred in CA group while the damage was significantly reduced in UTI group.　Conclusions　Ulinastatin can attenuate brain injury after asphyxiating CA/CPR in rats via inhibiting the expressions of IL-6 and IL-8, which may be related to suppressing activation of ERK1/2 and Akt.