Objective:To investigate the effects of Xingnao Yisui Decoction on the behaviour of vascular dementia (VaD) rats and the apoptosis of neurons in the CA1 region of the hippocampus; To explore its mechanism of action.Methods:Totally 60 adult SD rats with similar levels of cognitive function were selected and divided into Xingnao Yisui Decoction high-, medium- and low-dosage groups, donepezil group, model group and sham-operation group according to the random number table method, with 10 rats in each group. Except for the sham-operation group, the VaD model was prepared using a modified bilateral common carotid artery ligation method in all the groups. Xingnao Yisui Decoction high-, medium- and low-dosage groups were gavaged with 19.62, 9.81, 4.91 g/(kg·d) of Xingnao Yisui Decoction respectively, the donepezil group was gavaged with 0.5 mg/(kg·d) of donepezil solution, and the sham-operation group and the model group were given equal amount of saline gavage, 1 time/d for 4 weeks. Morris water maze experiment was used to observe the behavioral changes in each group, TUNEL staining was used to observe the apoptosis of neurons in CA1 area of hippocampus. Realtime PCR was used to detect the mRNA expression of NF-κB and MMP-9. ELISA was used to detect the changes of serum NF-κB, MMP-9, p53, Bcl-2 and Bax protein levels.Results:Compared with the model group, the escape latency of rats in the donepezil group and Xingnao Yisui Decoction high-, medium- and low-dosage groups was shortened ( P<0.05); the times of crossing the platform and the stay time in the target quadrant increased ( P<0.05); the number of apoptotic cells in hippocampal CA1 region decreased ( P<0.01); the number of apoptotic cells in hippocampal CA1 region decreased ( P<0.01); the mRNA expression of NF- κB and MMP-9 in hippocampal mRNA level decreased ( P<0.01); the content of NF-κB, MMP-9, p53 and Bax decreased ( P<0.01), while the content of Bcl-2 increased ( P<0.01). Conclusion:Xingnao Yisui Decoction can effectively mediate the NF-κB-MMP-9 pathway to improve the permeability of the blood-brain barrier and regulate p53-Bcl-2-Bax to reduce apoptosis of neurons in CA1 area of hippocampus, thus significantly improve the learning and memory ability of VaD rats.