Abstract: OBJECTIVE To explore the effect and mechanism of ulinastatin on brain injury in rats with hemorrhagic shock. METHODS Thirty-six ♂ SD rats were randomly divided into control group, model group and observation group, 12 rats in each group. The control group was given sham operation, the model group was not treated after modeling, and the observation group was given ulinastatin intravenous infusion after modeling. The mean arterial pressure(MAP), pH, base excess(BE) and lactic acid concentration(La) at the beginning of blood collection, the end of blood collection, the beginning of reinfusion and the end of reinfusion during modeling were recorded. The activity of superoxide dismutase(SOD) and the content of malondialdehyde(MDA) in hippocampus were measured 24 hours after the establishment of the model. The expression of SIRT1 and PGC-1α in hippocampus were measured by Western blotting. RESULTS There was no significant difference in MAP between groups at the beginning of blood collection and at the end of reinfusion. At the end of blood collection and the beginning of reinfusion, the MAP in the model group and the observation group was significantly lower than the control group(P<0.05). There was no statistical difference in pH, BE and La between the three groups at the beginning of blood collection. Compared with the control group, at the end of blood collection and the beginning of reinfusion, the pH, BE decreased, the La increased in the model group and observation group(P<0.05). At the end of reinfusion, there was no statistical difference in pH among the three groups, compared with the control group, the BE decreased, the La increased in the model group and observation group(P<0.05). The activity of SOD in the three groups from high to low were control group, observation group and model group, the difference was statistically significant(P<0.05). The content of MDA in the three groups from high to low were model group, observation group and control group, the difference was statistically significant(P<0.05). Western blotting showed that SIRT1 and PGC-1α protein expression levels were from low to high in the control group, model group and observation group. CONCLUSION Ulinastatin can promote the expression of SIRT1 and PGC-1α protein in hippocampus, achieve the effect of anti oxidative stress, and play the role of protecting the brain injury of ischemia-reperfusion rats.