Objective：To explore the effects of glutamine synthetase (GS) inhibitor on the homoeostasis of amino acid neurotransmitters and monoamine neurotransmitters in the striatum of mice. Methods：Three-month-old C57BL/6J mice were intraperitoneally injected with glutamine synthetase inhibitor-methionine sulfoximine (MSO) for 2 weeks (0.1 mL/10 g，qod). The protein levels of GS and glutamate transporters were detected by Western blot. The concentrations of amino acid neurotransmitters (glutamic acid and glutamine) and monoamine neurotransmitters (dopamine and 5-hydroxytryptamine) in the striatum were measured by high performance liquid chromatography. Results：Compared with the saline control group，MSO effectively inhibited GS protein expression and increased the levels of glutamate transporters (glutamate transporter 1 and glutamate aspartate transporter) in the striatum. Mice with MSO injection exhibited lower levels of glutamate，glutamine and aspartic acid，and higher levels of γ-aminobutyric acid and serine，but showed no change in the concentrations of monoamine neurotransmitters. Conclusion：Systematical inhibition of glutamine synthetase could affect the homoeostasis of metabolism of amino acid neurotransmitters in the brain of mouse，and lead to the decrease of the excitatory neurotransmitter glutamate level and the increase of inhibitory neurotransmitter γ-aminobutyric acid level.