Abstract: OBJECTIVE To investigate the relationship between the improvement of cognitive symptoms correlation function and the degree of Tau protein phosphorylation in Parkinson disease (PD) treated by l-stepholidine.METHODS One hundred and fifty rats were randomly divided into 3 groups, including blank control, MPTP group, drug group, 50 rats in each group. The PD rats model were established with MPTP. The body weight of rats were determined, than the latency time and the percentage of the swimming time through the Water Maze, the number and diameter of the apical dendritic branches in the hippocampal pyramidal cells were compared. The hippocampal neurons of rats were collected and the phosphorylation of P-Tau protein was calculated by enzyme linked immune sorbent assay (ELISA) method. Finally, the hippocampal tissues of rats were collected, and the apoptosis rate of hippocampal neurons was measured by flow cytometry.RESULTS Compared with the control group, the body mass, percentage of swimming time, the number the apical dendritic branches and the expression of P-Tau protein in MPTP group were significantly decreased in drug group (P<0.05), while the latency time was significantly prolonged(P<0.05), and the apoptosis rate of hippocampal neurons was increased significantly(P<0.05). Compared with MPTP group, the body mass, percentage of swimming time, the number of the apical dendritic branches in the hippocampal pyramidal cells and the expression of P-Tau protein in hippocampus were increased significantly in drug group (P<0.05), while the the latency time and cell apoptosis rate decreased significantly (P<0.05).CONCLUSION l-stepholidine has protective effects on rats model of PD, hyperphosphorylation of Tau protein is the possible mechanism of inhibition of l-stepholidine protects dopaminergic neurons.