To assess the usefulness of serum S100B as a biomarker, the present study proceeded by observing serum S100B kinetics in a rat transient middle cerebral artery occlusion (MCAO) model, then assessed the correlation between serum S100B and both brain edema formation and neurological outcomes. Study results showed increases in serum S100B concentrations, peaking 48 h after MCAO. Brain water content in the ipsilateral hemisphere significantly increased from 24 h after MCAO, and reached peak value 72 h after MCAO. A single measurement of serum S100B 48 h after MCAO showed significant correlations with maximal extent of brain edema 72 h after MCAO. Furthermore, S100B concentrations 48 h after MCAO significantly correlated with infarct volumes. Neurological outcomes were estimated in a long-term study, where a gradual recovery was observed up to 168 h after MCAO. Serum S100B 48 h after MCAO was found to show higher correlation with neurological score 168 h after MCAO than those 48 h after MCAO. These findings suggest that serum S100B is an effective biomarker in predicting both extent of brain edema and long-term neurological outcomes in a rat transient MCAO model.