The effects of Radix Salviae Miltiorrhizae (RSM) on extracellular adenosine (Ade) and its metabolites, i.e. inosine, hypoxanthine and xanthine, were studied with microdialysis and HPLC techniques during cerebral ischemia-reperfusion induced by 4-vessel occlusion in rat brain. Histological examination of hippocampus was performed 6 h after reperfusion. ECF (extracellular fluid) adenosine and its metabolites were compared between the controls (n = 6) and RSM-treated rats (n = 6). Basal level of Ade and its metabolites release were not greatly affected by pretreatment with RSM, and no significant difference as compared with the sham-operated (n = 6). Ade and its metabolites were dramatically increased after ischemia, and decreased near basal-level and its metabolites remained high at the end of reperfusion. In the RSM-treated animals, the tendency of changes of Ade and its metabolites was just the same as in the controls, but the magnitudes of changes were significantly lower at some different time points. In sham-operated animals, no changes were observed at different time points both during ischemia (30 min.) and reperfusion (60 min.). Histopathological findings demonstrated that RSM pretreatment results in better histologic preservation of the pyramidal cells in the postischemic reperfusion CA1 sector both qualitatively and quantitatively. These results indicated that RSM protects against cerebral ischemia reperfusion injury.