Objective To evaluate the effects of ulinastatin on mild and severe intestinal ischemia/reperfusion(I/R) injuries of mice. Methods Intestinal I/R injury models for ischemic time of 90 min (model 1) and 180 min (model 2) were established. Adult male C57BL/6 mice were randomly divided into 6 groups (n=10 each), i.e. the normal control group, sham operation group, model 1 control group, model 1 treated group, model 2 control group, and model 2 treated group. Mice of the model 1 treated group and model 2 treated group were injected i.v. with ulinastatin (16 IU/g) after the ischemia and before the reperfusion. Mice of the model 1 control group and model 2 control group were injected with the same volume of normal saline at the same period of time. The blood of inferior vena cava was collected after two hours of reperfusion. Injuries of small intestinal mucosa were observed and the degrees of pathological injury of small intestine were scored by the Chiu scoring. The activity of myeloperoxidase (MPO) was detected and serum TNF-α and IL-6 levels were determined by the ELISA. Results The structure of small intestinal mucosa of the normal control group and sham operation group was normal. The small intestinal mucosa of other groups was significantly injured and the activity of MPO and levels of serum TNF-α and IL-6 were increased. Compared to the model 1 control group, injuries of small intestinal mucosa of the model 1 treated group were significantly severer and Chiu scores were significantly higher (P<0.01). While compared to the model 2 control group, injuries of small intestinal mucosa of the model 2 treated group were significantly milder and Chiu scores were significantly lower (P<0.01). The activity of MPO and levels of serum TNF-α and IL-6 of the model 1 treated group and model 2 treated group were significantly lower than those of relevant control groups. The differences were statistically significant (P<0.01). Conclusion Ulinastatin can relieve severe I/R injuries while aggravate mild I/R injuries. This may be relevant to its anti-inflammation effect.