Objective To explore whether glutamine can ameliorate oxidative stress injury in mice with sepsis in order to provide an experimental basis for clinical application.Methods Thirty 5-week old Qunming male mice were randomly divided into three groups: control, model and glutamine groups, 10 mice in each group. Lipopolysaccharide (LPS) 5 mL/kg was injected into intraperitoneal cavity to establish septic model in model and glutamine groups, and an equal amount of normal saline was injected into the cavity in control group. After the septic model was successfully established, propylene ammonia acyl-glutamine 0.75 g/kg was immediately injected through tail vein in the glutamine group, and an equal amount of sterile normal saline was injected into the vein in the model and control groups. After 6 hours, the experiment was terminated, the blood was collected from the orbital cavity and the animal was sacrificed; serum, liver and renal tissue homogenates were taken to detect the indexes of oxidative stress, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and lipid metabolite malonaldehyde (MDA).Results Compared with the control group, the levels of SOD activities and GSH-Px of serum and liver, kidney tissue in the model group were significantly lower, and the MDA content was significantly higher. Compared with the model group, the levels of SOD activities and GSH-Px of serum and liver, kidney tissue in the glutamine group were significantly higher, and the MDA content was significantly lower [SOD in the serum (U/mL): 134.78±3.74 vs. 124.60±3.49, SOD in the liver (U/mg): 56.71±1.35 vs. 49.84±0.86, SOD in the kidney (U/mg): 46.22±1.22 vs. 43.22±1.52; GSH-Px in serum (U/mL): 325.15±21.86 vs. 267.04±13.5, GSH-Px in liver (U/mg): 91.35±1.59 vs. 83.40±1.33, GSH-Px in kidney (U/mg): 136.08±0.58 vs. 132.97±0.74; MDA in serum (μmol/L): 9.20±0.32 vs. 13.67±1.24, MDA in liver (nmol/mg): 1.85±0.10 vs. 4.88±0.17, MDA in kidney (nmol/mg): 2.47±0.12 vs. 3.52±0.27, allP < 0.01].Conclusion Sepsis can cause oxidative stress and oxidative damage, glutamine not only can improve the levels of antioxidant enzymes of GSH-Px and SOD, enhance antioxidant capacity, reduce the MDA content of lipid metabolites, but also can reduce the toxic metabolites, so as glutamine has the effect of ameliorating oxidative stress injury.