Objective To investigate whether there is a sex difference in the offspring of Inflammatory Bowel Disease (IBD) mice with IBD. Methods BALB/c female mice were randomly divided into normal control and IBD groups. The mice in the normal control group drank autoclaved water freely, and the IBD group drank 2% Dextran sodium sulfate (DSS) for 7 days and then switched to autoclaved water for 10 days for 3-4 cycles, and at the same time, they were mated with healthy males. When the pups were 8 weeks old, they were divided into the Con group and IBD group, and the IBD group drank 3% DSS for 7 days. Disease activity index was scored by monitoring body weight, fecal consistency and blood in stool; pathological sections of colon tissues, changes in cup cells and mucus layer were observed; interleukin-6 (IL-6), IL-1β, IL-33, and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA); the real-time fluorescence quantitative PCR was used to determine the mRNA expression levels of tight junction proteins and MUC-2 in the colon. Results Compared with the IBD female mice, IBD male mice had higher DAI scores, significantly shorter colons, large inflammatory infiltrates, crypt abnormalities, and absence of cup cells in the colon, significantly lower relative mRNA expression of OCLN, significantly higher levels of IL-6 and IL-33, and significantly lower levels of IL-10. Conclusion The symptoms of colitis in the offspring of IBD mice were more severe in males than in females, which was mainly related to the severe impairment of the intestinal epithelial barrier function.