The aim of this study was to investigate the effect of 30 min forebrain ischemia, followed by 120 min reperfusion on extracellular fluid (ECF) levels of dopamine (DA), norepinephrine (NE), serotonin (5-HT) and their metabolites, homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the striatum of gerbils, so as to obtain further information on the mechanism of Radix Salviae Miltiorrhizae (RSM)-induced neuroprotection. Microdialysis was used to sample the extracellular space. Dialysate was measured by high performance liquid chromatography with electrochemical detector (HPLC-ED). ECF DA, NE levels increased from basal levels by 282, 227 and 221 folds, by 9.14, 8.51 and 8.25 folds, respectively for the three ischemic duration (0-10; 11-20; 21-30 min). ECF DA, NE, 5-HT levels in the RSM-treated group were significantly decreased as compared with those in the control group during ischemia (P < 0.01). The results suggested that monoamine neurotransmitters were involved in ischemic neuron damage directly or indirectly; and that RSM plays a protective role during cerebral ischemia by attenuating the dysfunctions of monoamine neurotransmitters.