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Ethnopharmacological relevance: Dan-Chuan-Hong (DCH) whose herbs are Salvia miltiorrhiza Bge,Ligusticum chuanxiong Hort,and Cartha-mus tinctorius L.is an effective traditional Chinese medicine (TCM) formula for treating traumatic brain injury (TBI).Aim of the Study: To investigate whether absorbed Hydroxysafflor yellow A (HSYA) following oral DCH to rat with TBI induced acute neuroprotection similar to DCH via antioxidative pathway.Materials and Methods: By Ultra-high Performance Liquid Chromatography with Tandem mass spectrometry (UPLC-MS/MS) HSYA was detected in brain following oral administrtion of DCH to TBI rats.Then Sprague-Dawley rats with TBI were divided into sham TBI,TBI+Vehicle,TBI+DCH and TBI+HSYA groups.The samples of cerebral cortex in each group were collected at 6,12 and 24 hour after traumatic brain injury and analyzed for their oxidant-antioxidant status.Results: HSYA (m/z,611→491.04 or 611→325.06) in water extract of DCH was determined at 2.74±0.02 min in brain sample tissue.DCH and HSYA group reduced the level of malondialdehyde (MDA),increased the activities of superoxide dismutase (SOD),catalase (CAT),and the contents of glutathione (GSH),GSH/GSSG ratio in cerebral cortex.There was no statistical significant compared each other (p>0.05).Conclusions: HSYA,when absorbed into brain following oral DCH to rat with TBJ,induced significantly acute neuroprotection similar to DCH via the antioxidation pathways,suggesting the representative compound for DCH in fighting TBI.