Objective To investigate the neuroprotective effect of tetrahydroxystilhene glucoside (TSG), an effective component of Polygonum multiflorum thunb., in rats after cerebral ischemia/reperfusion (I/R) and its action mechanism.Methods Healthy male Sprague-Dawley rats weighting 250-350 g were divided into control, model, low-dose TSG (60 mg/kg/d), and high-dose TSG (120 mg/kg/d) groups, 24 each. A rat model of middle cerebral artery occlusion was established by Longa's method, and the neurological behavior was evaluated by Longa's scoring. Rats were sacrificed at 6 hrs, 24 hrs, 48 hrs, and 7 days after reperfusion in the cerebral cortex, and the apoptosis of nerve cells was detected by terminal deoxynucleotidyl transferase-mediated nick-end labeling. Meanwhile, the mRNA and protein expression of TrkA and Bcl-2 was measured by in situ hybridization and immunohistochemistry, respectively.Results All rats treated by I/R showed marked neurological deficit symptoms at all time points after reperfusion. Compared with the model group, the two TSG groups had significantly lower neurological deficit scores at 24 hrs, 48 hrs, and 7 days after reperfusion (P<0.05), as well as significantly reduced numbers of apoptotic cells and significantly increased mRNA and protein expression of TrkA and Bcl-2 at all time points after reperfusion (P<0.05 for both).Conclusions TSG improves the neurological function and reduces the number of apoptotic cells in rats after cerebral I/R, probably by increasing the expression of TrkA and Bcl-2.