The aim of this study was to investigate the mechanism of action underlying the effect of polysaccharide from Vitis vinifera L. (VTP) on the nuclear factor kappa B/inhibitor kappa B alpha (NF-kB/IkB-a) signaling pathway and related inflammatory factors in hippocampus of rats with Alzheimer's disease (AD). Amyloid-b 25-35 was injected into the hippocampus to establish AD model rats, and the rats were administered with donepezil and VTP. The levels of interleukin-1b, interleukin-6 and tumour necrosis factor-a in the serum were determined by enzyme-linked immunosorbent assay. The phosphorylation level, protein and gene expression of NF-kBp65 and IkB-a in hippocampus were detected by immunohistochemistry, western blot and real-time quantitative polymerase chain reaction (PCR), respectively. VTP effectively improved the learning and memory ability of AD rats. Transmission electron microscopy indicated that VTP reduced the toxic effects of amyloid-b 25-35 on neurons in AD rats. Enzyme-linked immunosorbent assay showed that VTP inhibited the expression of interleukin-1b, interleukin-6 and tumour necrosis factor-a in a dosedependent manner. Compared with the model group, the expression levels of NF-kBp65 in the nucleus of the VTP group decreased, which was consistent with the Western blotting results. The expression of p-IkB-a and IkB-a, and, the mRNA level of NF-kBp65 and IkB-a in VTP group were significantly decreased compared to that in the model group, indicating that VTP has a therapeutic effect on AD. Its mechanism may be related to the inhibition of inflammatory response.