Objective To investigate the serum concentration and expressions of S100β protein in hippocampus CA1 region and the changes of water content in rats with asphyxia following ulinastatin injection after cardiopul-monary resuscitation (CPR). Method One hundred twenty male adult SD rots were randomly divided into 3 groups:sham-operation group, CPR group and ulinastafin group. And each group was further divided into 5 sub-groups (n=8) based on various intervals, 0.5 h,3 h,6 h,12 h and 24 h after tracheotomy in sham-operation group or after ROSC in CPR group and ulinastatin group. Asphyxial cardiac arrest and CPR model of rat was used in CPR group and ulinastatin group in which bolus dose of 100 000 U/kg ulinastatin was injection into arteria carotis. Anaesthesia, tracheotomy and vascular canratlafion without asphyxia and CPR in sham-operation group. Samples from subgroups were taken at different intervals. Brain water content was measured by using wet-dry weight method. Serum S100β protein was measured with enzyme-linked immunosorbent assay ( ELISA). The expres-sion of S100β protein in hippocampus CA1 region was measured by using immunohistochemistry. Data were ana-lyzed by SPSS version 10.0 software. Results Compared with sham-operation group, the brain water content of rats elevated significantly in all CPR subgroups after ROSC (P<0.05 or P<0.01). The brain water content of rats decreased significantly 12 h and 24 h after ROSC in ulinastatin group in comparison with CPR group (P<0.05). The serum S100β protein started to elevated significantly 0.5 h after ROSC in CPR group, and reached the peak 12 h after ROSC (P<0.01).serum S100β decreased 6 h,12 h and 24 h after ROSC in ulinastatin group compared with CPR group (P<0.01).The expression of S100β protein in hippocampus CA1 region remained at a low level in sham-operation group. The expression of S100β protein elevated significantly in all CPR subgroups after ROSC compared with sham-operation group (P<0.05 or P<0.01). Compared with CPR group, the ex-pression of S100β protein decreased after ROSC in ulinastatin group(P<0.05) .However,the expression of S100β protein in hippocampus CA1 region was significantly correlative with brain edema in all subgroups of CPR (r=0.862, P<0.05). Conclusions Ulinastatin can decrease serum S100β protein and the expression of S100β pro-tein in hippocampus CA1 region and lessen the severity of cerebral edema, alleviate the brain isehemic injury in rats after cardiopulmonary resuscitation.