Objective:To study the role of microbial-derived antioxidants (MA) based on the model of diquat-induced oxidative stress, endoplasmic reticulum stress, apoptosis and function in mice.Methods:18 female C57BL/6 mice with body mass of 16~18 g were selected and randomly divided into 3 groups with 6 mice in each group. After 22 days of feeding, model and antioxidant group mice were intraperitoneally injected with diquat solution and control group were injected with same amount of isotonic saline. The content of free radical, MDA, antioxidant enzyme activity, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity were detected according to the instructions of the kit. QRT-PCR was used to detect the expression of endoplasmic reticulum stress and apoptosis-related genes. One-way analysis of variance was used for data comparison between groups.Results:Hydrogen peroxide (H 2O 2) in the control group, model group and antioxidant group was (8.74 ± 1.38), (11.44 ± 1.01), (9.81 ± 0.98) mmol/g prot, respectively, and the difference between the groups was statistically significant ( F = 7.640, P < 0.05). MDA content in the control, model and antioxidant group were (0.65 ± 0.07), (0.86 ± 0.18), (0.70 ± 0.05) nmol/mg prot, respectively, and the difference between the groups was statistically significant ( F = 5.406, P <0.05). Aspartate aminotransferase (AST) activity in the model group (146.68 ± 4.29) U/gprot was significantly higher than control group (125.64 ± 15.69) U/gprot and antioxidant group (126.57 ± 1.82) U/gprot, F = 6.192, P < 0.05. Real-time quantitative PCR result showed that the relative expression of protein kinase R-like endoplasmic reticulum kinase (PERK) and activated transcription factor 6 (ATF6) genes in the model group was significantly higher than control group, which were 1.880 ± 0.442 and 1.800 ± 0.380, F = 7.702 and 10.815, and P < 0.05, respectively. Apoptosis-related gene expression results showed that the relative expression levels of caspase3 and caspase8 genes in the antioxidant group (1.136 ± 0.381 and 1.593 ± 0.407) was significantly lower than model group (1.572 ± 0.127 and 2.843 ± 0.973), ( F = 12.800, 7.657, P < 0.05). Conclusion:Microbial-derived antioxidants can reduce diquat-induced liver oxidative stress, endoplasmic reticulum stress and hepatocyte apoptosis in mice, and thus improves liver function.