OBJECTIVE To investigate the effects of gensenoside Rg1 on expressions of phosphorylated tau protein (P-tau), protein phosphatase 2A (PP2A) and tau protein in Alzheimer's disease-like tau phosphorylation rat brain slices, and to explore the mechanisms of gensenoside Rg1 in inhibiting tau phosphorylation. METHODS Brains of 5-week-old Wistar rats were cut into slices which were 400 μm thick. These brain slices were randomly divided into blank control group, untreated group, low-dose ginsenoside Rg1 group, medium-dose ginsenoside Rg1 group and high-dose ginsenoside Rg1 group, with 10 slices in each group. All brain slices were cultured with artificial cerebrospinal fluid (ACSF). And brain slices in the ginsenoside R1 groups were administered with ginsenoside Rg1 (60, 120 and 240 μmol/L respectively) in ACSF for 2 h firstly. After 2-hour culture, okadaic acid (OA) was administered into ACSF of the untreated group and the ginsenoside Rg1 groups separately for 3 h to induce tau phosphorylation to prepare AD models. The concentration of OA in each group was 1 μmol/L. There was no any intervention for the brain slices in the blank control group. Expressions of P-tau, PP2A and tau proteins in the brain slices were determined by immunohistochemical method, and the results were analyzed by image acquisition and analysis system. RESULTS Compared with the blank control group, the expression of P-tau protein was significantly increased (P<0.01) and the expressions of tau and PP2A proteins were decreased (P<0.01, P<0.05) in the untreated group. Compared with the untreated group, the expression of P-tau was significantly decreased (P<0.01) and the expressions of tau and PP2A proteins were increased (P<0.01, P<0.05) in the ginsenoside Rg1 groups, especially in the high-dose ginsenoside Rg1 group. CONCLUSIONS Ginsenoside Rg1 can promote dephosphorylation of P-tau by increasing the expression of PP2A in Alzheimer's disease-like tau phosphorylation rat brain slices, so as to inhibit tau phosphorylation.