Objective To determine the protective roles of lycium barbarum polysaccharide on methyl mercury chloride-induced injury for neuronal differentiation of hippocampal neural stem cells(NSCs). Methods NSCs were collected from the hippocampus of 16-embryonic day Sprague-Dawley rats. The cells were cultivated in neural stem cell-specific medium for 10 days. The neurospheres were dissociated into single cells and cultured in the 24-well plates with poly-L-lysine-coated cover glass. Cells were divided into four groups: a control group in which the cells were cultured in DMEM/F12 medium; a lycium barbarum polysaccharide group-the cells were cultured in DMEM/F12 with lycium barbarum polysaccharide; a methyl mercury chloride group-the cells were cultured in DMEM/F12 with methyl mercury chloride; Methyl mercury chloride + lycium barbarum polysaccharide group-the cells were cultured in DMEM/F12 with methyl mercury chloride and lycium barbarum polysaccharide. The cell growth and differentiation were determined by immunostaining against MAP-2 or GFAP antibody.Results The percentage (3.63%±0.62%) and average perimeter (63.36μm±5.57 μm) of the differentiated neurons in the methyl mercury chloride group were lower than that in the control group, while the percentage (7.75%±0.59%) and average perimeter (253.3μm±11.21μm) of them in lycium barbarum polysaccharide group were much more than all other groups. Compared with the methyl mercury chloride group, after methyl mercury chloride treatment the lycium barbarum polysaccharide increased the neuronal differentiation (5.92%±0.98%) to the level in control group and their average perimeter (111.9μm±6.07μm) in this group also showed 2-fold increase. Conclusion Lycium barbarum polysaccharide promotes the NSCs to