AIM To study correlation of medicine ingredients and neurotransmitters in brain interstitial fluid (BIF) of cerebral ischemic rats.METHODS Sprague-Dawley rats (n =12) were randomized into two groups.Rats in SLT (Sailuotong capsule) group were administrated with SLT(150 mg·kg-1) by garage and model rats were administrated with distilled water for 7 d before middle carotid artery occlusion (MCAO).Rats BIF samples were collected by microdialysis and rats suffered from permanent cerebral ischemia during sampling under isoflurane anesthesia.LC-MS/MS was employed for medicine ingredients detection while HPLC-ECD system for neurotransmitter determination.Computational study was pursued for the correlation of certain endogenous and exogenous substances in ratsBIF.RESULTS Three medicine ingredients from SLT were detected by LC-MS/MS, namely bilobalide (BB), crocin and ginkgolide A (GA).These ingredients comes from Folium Ginkgo and Stigma Croci, which are two herbs composition of SLT.Four neurotransmitters were determined by HPLC-ECD system, namely serotonin (5-HT), dopamine (DA), glutamate (Glu), γ-amino butyric acid (GABA).Neurotransmitter levels in rats BIF of SLT group were significantly lower than that of model group.Computeraided correlation analysis showed that dynamic change of BB and GA were highly correlated with four neurotransmitter level changes.CONCLUSION SLT down-regulate both monoamines and amino acids levels, which increase dramatically after rats subjected to MCAO.Data suggests, maybe, SLT protect ischemic brain by down regulating over-released neurotransmitters.Computer aided correlation study suggests BB and GA are the most likely effective ingredients for regulating the neurotransmitters.