Abstract: Objective: The protective effect of Poria cocos polysaccharides (PCPs) on the learning and memory function of scopolamine-induced dementia mice and its mechanism were explored, which was expected to provide a new idea for the prevention and treatment of dementia. Methods: Mice were divided into control group, model group, low-dose PCPs group (50 mg/kg), high-dose PCPs group (100 mg/kg), and donepezil group (1 mg/kg). The mice were administered by gavage once daily, continuously for 28 d, in which mice except those in the control group were intraperitoneally injected with scopolamine (1 mg/kg) from the 24^th d, successively for 5 d. The learning and memory function of mice were observed by water maze test, the pathological changes in the hippocampal tissue were examined by hematoxylin and eosin (HE) staining, the apoptosis of hippocampal cells was observed by TUNEL staining, the expression of hippocampal apoptosis-related genes was detected by real-time quantitative PCR, the hippocampal central cholinergic system indicators and oxidative stress indicators were detected by enzyme-linked immunosorbent assay (ELISA), and the expression of Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the hippocampal tissue was detected by Western blot. Results: Compared with that in the model group, the escape latency of mice in low-dose and high-dose PCPs groups was shortened (P<0.01), the residence time in the target quadrant was prolonged and the number of times of crossing platform was increased (P<0.01), and the pathological change in the hippocampus tissue was alleviated; the apoptosis rate of neurons was reduced (P<0.05, P<0.01), the mRNA expression of B cell lymphoma-2 (Bcl-2), the activity of choline acetyltransferase (ChAT) and the content of acetylcholine (ACH) were increased (P<0.05, P<0.01), the mRNA expression of Bcl-2 associated X protein (Bax) and the activity of acetylchohnesterase (AChE) were reduced (P<0.05, P<0.01); the activity of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and the expression of Nrf2 and HO-1 were increased (P<0.01), the content of malondialdehyde (MDA) and the expression of Keap1 were decreased (P<0.05, P<0.01). Conclusion: PCPs can protect the learning and memory function of scopolamine-induced dementia mice, and its mechanism may be related to its anti-apoptosis of neurons, regulation of central cholinergic system and inhibition of oxidative stress.