Objective To investigate the correlation of serum S100B expression with behavioral tests and cerebral edema.Examine the changes of perihematoma tissue ultra microstructure in the development of brain edema.Methods A rat model of brainstem hemorrhage was established using the stereotactic technology, serum S100B was detected by double antibody sandwich ELISA, Brain water contents were measured by dry-wet weigh method.Perihematoma tissue ultra microstructure was observed under the electron microscope.Results Compared with the sham operated group, The S100B protein level in serum, behavioral scores and brain water content increased in the brainstem hemorrhage group at 6 hours, reached a peak at 48 hours, then decreased gradually.The S100B protein level in serum, brain water content, behavioral scores were positively correlated with each other (P＜0.05).Perihematoma tissue was observed under the electron microscope: stellate cells and their surrounding foot process mild swelling at 6 hours, Stellate cells visible swelling, partial cytoplasm showed vacuoles sample change, myelin part dissection, had mitochondria crest fault and vacuoles at 48 hours.Conclusions The S100B protein level in serum, brain water content, behavioral scores were positively correlated with each other.This suggests that cerebral edema may be developed through the high S100B protein level after brainstem hemorrhage.