Abstract：Objective: To observe the differences in gut microbiota of chronic unpredictable mild stress (CUMS) - induced depression model rats in different genders, and provide experimental evidence for exploring the gender differences in the onset of depression. Method: 32 healthy SD rats were randomly divided into four groups based on gender: male blank group, male model group, female blank group, and female model group, with 8 rats in each group;The blank group was fed without any stimulation method, while the model group was replicated using the 28 day CUMS induced depression method. After successful model preparation, fresh feces from all rats were collected for high-throughput 16S-RNA sequencing;Behavioral observations were conducted before and after preparing the model.Result: There were statistically significant differences between the blank group and the model group in the sucrose preference experiment, open field experiment, and forced swimming; the sucrose preference experiment showed that there were gender differences in the CUMS model rats, while the open field experiment and forced swimming experiment did not show gender differences.The analysis of gut microbiota genera showed that compared with the blank group, the alpha and beta diversity of the CUMS group showed an upward trend.The ratio of Firmicutes/Bacteroidetes in male CUMS rats, as well as the richness of the genus Roche and the family Trichomycteridae in the NK4A136 group, decreased, while females showed an increasing trend. Conclusion:The ratio of Firmicutes/Bacteroidetes of different genders in the gut microbiota may be a key factor in the onset of depressionr, and the Roche genus and the Trichomycteridae NK4A136 group may be potential factors in correcting gut microbiota and improving symptoms of depression.