Abstract: Objective To investigate the effects and mechanism of silibinin on learning and memory in mice with Alzheimer's disease.Methods Alzheimer's disease model was established by intracerebroventricular injection of amyloid protein β(Aβ_1-42)in 50 mice and then the mice were randomly divided into a control group, a model group, 2 silibinin groups(100 and 200 mg/kg), and a positive control group(1.3 mg/kg of donepezil).Learning and memory of the mice was evaluated with Y maze test.Western blot and enzyme-linked immunosorbent assay(ELISA)were adopted to detect the expressions of tumor necrosis factor alpha(TNF-α), interleukin-1 beta(IL-1β), interleukin-6(IL-6), and interleukin-4(IL-4).Results Compared with those of the control group, the preference index of novel object recognition test at one hour(0.53±0.09)and 24 hour(0.51±0.12)and spontaneous alternation response rate of Y maze test(0.52±0.09%)decreased significantly for the mice in the model group(P<0.01).Compared with those of the model group, the preference index of novel object recognition test at one hour(0.67±0.11)and 24 hour(0.69±0.11)and spontaneous alternation response rate of Y maze test(0.72%±0.09%, P<0.01)increased significantly for the mice in 200 mg/kg silibinin treatment group.Compared with those of the control group, the level of IL-4 decreased, but TNF-α and IL-1β increased significantly in hippocampus of the mice of the model group(all P<0.01).Compared with those of the model group, the level of IL-4 increased, but TNF-α and IL-1β decreased in hippocampus of the mice of 200 mg/kg silibinin treatment group.Conclusion Silibinin could improve learning and memory disorder of the mice with intracerebroventricular-Aβ_1-42 injection and the effects may be related to the regulation of inflammation factors in the brain.