Objective To explore the anti-aging effects of angelica sinensis polysaccharides(ASP) on brain aging induced by D-galactose in Nestin-green fluorescent protein (GFP )transgenic mice and its mechanism. Methods Male Nestin-GFP transgenic mice (n=40) aging from 6 to 8 weeks old were randomly divided into the normal, ASP normal, brain aging model and ASP brain aging model groups. The brain aging model group was subcutaneously injected with D-galactose (200 mg/kg), qd×42 days. The ASP brain aging model group was intraperitoneally injected with ASP (140 mg/kg) since the 16th day of the replication in the brain aging model, qd×27 days. The ASP normal group was subcutaneously injected with the same amount of saline, qd×15 days, and following intraperitoneally injected with ASP (140 mg/kg) qd×27 days. The normal group was subcutaneously injected with an equal volume of saline within the same time. The related experiment was performed on the second day after finishing copying the model. Learning and memory abilities were measured by Morris water maze. Frozen sections were made to observe the hippocampus fluorescence intensity. The number of senescent cells were detected by senescence-associated β-galactosidase (SA-β-Gal) staining. The activities of superoxide dismutase (SOD), total antioxidant capacity (T-AOC) and contents of malonaldehyde (MDA) in hippocampus were quantified by chromatometry. The level of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α proinflammatory cytokines in hippocampus were detected by methods enzyme-linked immunosorbent assay (ELISA). Results In the brain aging model group, the spatial learning and memory capacities were weaken, the fluorescence intensity decreased in the dentate gyrus (DG) of hippocampus, SA-β-Gal positive granules increased in section of brain tissue，and the activity of SOD, T-AOC decreased in hippocampus while the contents of MDA increased in hippocampus. The level of IL-1β, IL-6 and TNF-α increased in hippocampus. Compared with the brain aging model group, the spatial learning and memory capacities in the ASP brain aging group, were enhanced, the fluorescence intensity increased in the DG area of hippocampus, SA-β-Gal positive granules decreased in section of brain tissue, and the activity of SOD, T-AOC increased in hippocampus while the contents of MDA decreased in hippocampus. The level of IL-1β, IL-6 and TNF-α in hippocampus decreased. Conclusion ASP can antagonize brain aging induced by D-galactose in mice. In addition, improvement of antioxidant ability, down regulation of the level of proinflammatory cytokines and maintaining the number of neural stem cells in hippocampus may be the underlying anti-aging mechanism of ASP.