Objective To compare the effects of L-glutamic acid on cell viability and cell morphology of HT22 and SY5Y with different treatment times and concentration， so as to provide reference for the construction of cell injury model induced by L-glutamate. Methods HT22 and SY5Y cells were treated with 0， 0.25， 0.5， 1， 2， 5， 10， 15， 20， 25 mmol/L L-glutamate. After 24 hours， MTT and CCK8 methods were used to detect the activity of the two cells， and the leakage rate of lactate dehydrogenase（ LDH） in the cell culture medium was detected to observe the cell death. SY5Y cells and HT22 cells were treated with L-glutamate at different concentrations of 10 mmol/L and 5 mmol/L for 0， 2， 4， 8， 12， 18， 24， 36 and 48 hours. The effects of L-glutamate on the activity of SY5Y cells and HT22 cells at different incubation times were studied by MTT and CCK8 methods， and the morphological damage of L-glutamate was observed by the microscope. Results When the concentration of L-glutamate was 1， 2， 5， 10， 15， 20， 25 mmol/L， the activity of SY5Y and HT22 cells was lower than 0 mmol/L（ P＜ 0.05）； SY5Y and HT22 cells were treated with 10 and 5 mmol/L L-glutamate respectively. The activity of the two cells was lower than 0 h at 4， 8， 12， 18， 24， 36 and 48 h（ P ＜ 0.05）.When SY5Y cells were treated with 2， 10， 15， 20 and 25 mmol/L L-glutamate for 24 hours， the leakage rate of LDH was higher than 0 mmol/L（ P＜0.05）； The leakage rate of LDH in HT22 cells treated with 1， 2， 5， 20 and 25 mmol/L L-glutamate for 24 hours was higher than 0 mmol/L（ P＜0.05）. The cell activity of SY5Y cells treated with 10 mmol/L L-glutamate for 24 hours was（ 82.80±9.71）% by MTT assay， and the cell morphology showed mild damage. After HT22 cells were treated with 5 mmol/L L-glutamate for 24 hours， the cell activity was（ 72.01±5.33）%， and the cell morphology showed mild damage. Conclusions Treating HT22 cells with 5 mmol/L L-glutamate for 24 hours is an ideal modeling condition for HT22 cells， and treating SY5Y cells with 10 mmol/L L-glutamate for 24 hours is the ideal condition for SY5Y cells， which provides an experimental condition reference for the application of L-glutamate injury cell model to study the pathogenesis of nervous system diseases.