Abstract: Objective: The effects of calycosin on learning-memory behavior in aging mice induced by D-galactose were investigated in this study. Methods: The aging mice model was induced by subcutaneous injection of D-galactose ( 150 mg·kg^-1·d^-1) were established after 6 weeks.The D-galactose-induced aging mice were divided into model group, oxiracetam group ( 300 mg·kg^-1·d^-1) , and calycosin high, medium and low dose treated-groups ( 20, 12, 7 mg·kg^-1·d^-1) .Mice in the model group and normal control group were given normal saline. After intraperitoneal injection 7 d, the passive learning ability and memory capacity of mouse were investigated by the platform and the Y maze. Then organ index and antioxidant activity were detected, such as liver, spleen, thymus, brain and serum superoxide dismutase ( T-SOD) , glutathione peroxidase ( GSH-Px) , malondialdehyde ( MDA) and brain acetylcholinesterase ( Ach E) activity. Results: Compared with the model group, in the Y maze, the number of correct reaction and active avoidance rate of calycosin-treated mice were significantly increased ( p < 0.05) , and the escape period was significantly shortened and the number of errors in the step-down test was significantly reduced ( p < 0.05) . Compared with the model group, liver, spleen, thymus and brain organ index of calycosin-treated mice were significantly different ( p < 0.05) .In the calycosin groups, antioxidant enzyme ( T-SOD, GSH-Px) activity was significantly elevated ( p < 0.05) , MDA content was significantly reduced ( p < 0.05) , and brain tissue Ach E activity was decreased ( p < 0.05) . Conclusion: Calycosin can improve the learning-memory function of aging mice induced by D-galactose. The mechanism may be to increase the endogenous antioxidant enzyme activity, reduce lipid peroxidation damage, protect organ function such as brain, spleen and thymus and reduce brain tissue Ach E activity.