OBJECTIVE To observe the effects of schizandrol A on the learning and memory disorder in mice， and to explore its mechanism. METHODS The memory impairment model was established by using pentobarbital sodium（20 mg·kg-1）intraperitoneally injected in mice. Schizandrol A （0.5，1.0，2.0 g·kg-1·d-1） was administered through gavage for consecutive 14 d. Morris Water Maze test was used to evaluate the impairment of learning and memory. The activity of superoxide dismutase （SOD）， nitric oxide （NO） and catalase （CAT） of brain tissue were measured. The positive expression of nuclear transcription factor-κB （NF-κB）， choline acetyltransferase （ChAT）， brain-derived neurotrophic factor （BDNF） in the hippocampus CA1 region were determined by immunohistochemical analysis. At the cellular level， with schizandrol A （0.3，0.6，1.2 μmol·L-1） pre-administered 24 h， the PC12 cell apoptosis model was induced by H₂O₂. And PC12 cell activity was detected by thiazole blue （MTT） colorimetric assay， the activity of NO in cell serum were measured. The expression of bax was determined by combination of western blotting and image analysis software. The bcl-2 expression was detected by immunocytochemical staining. RESULTS Morris Water Maze test showed that， during the spatial probe trial on the fifth day， the mice in the model group had shorter residence time and less crossing times on the previous flat area than those in the control group （P <0.05）， which could be prolonged after schisandrin treatment （P＜0.05，P＜0.01）. Analysis of brain tissues showed that， compared with the control group， NO level increased and SOD， CAT activity decreased in the model group （P <0.01）. After being treated with schizandrol A， the NO level significantly decreased （P <0.01）， while SOD and CAT activity increased （P<0.01）.Immunohistochemistry analysis showed that the protein expression of ChAT and BDNF in the hippocampal CA1 region decreased in the model group， the protein expression of NF-κB significantly increased after modeling， while schizandrol A（1.0 g·kg-1） significantly increased the protein expression of ChAT and BDNF， and inhibited the protein expression of NF-κB（P＜0.05，P＜0.01）. At the cellular level， compared with the H₂O₂ model group， schizandrol A（0.6，1.2 μmol·L-1） significantly increased PC12 cell viability and decreased the NO level（P＜0.05，P＜0.01). Compared with the H₂O₂ model group， the expression of Bcl-2 in the schizandrol A group（1.2 μmol·L-1） was up-regulated and the expression of bax was down-regulated. CONCLUSION Schizandrol A could improve the learning-memory dysfunction in mice induced by sodium pentobarbital intraperitoneally injected， and its protective mechanism is related to the effect of lowering oxidative damage and inhibiting the cell apoptosis through up-regulating the expression of Bcl-2 and down-regulating the expression of bax and improving the synthesis of neurotransmitters through increasing the expression of ChAT in the hippocampal CA1 region.