Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterized by immune dysregulation and defective mucosal healing, predominantly affecting the colonic and rectal mucosa with diffuse inflammation and ulceration. Its pathogenesis involves genetic susceptibility, immune dysfunction, and environmental triggers. The regenerating gene (Reg) family, identified over four decades ago, is upregulated in IBD and has been implicated in anti-inflammatory responses, tissue regeneration, and mucosal barrier maintenance. Among these, Reg1 and Reg3 have been proposed as potential therapeutic targets due to their roles in promoting intestinal epithelial repair in both human and mice. In this study, we investigated the role of Reg1-3(Reg1, Reg2, Reg3a, Reg3b, Reg3d, Reg3g) genes using a dextran sulfate sodium (DSS)-induced UC mouse model. C57BL/6J wild-type (WT) and Reg1-3(Reg1, Reg2, Reg3a, Reg3b, Reg3d, Reg3g) knockout (Reg(-/-)) mice (6-11 weeks old; n=3-8 per group) were treated with 2 % DSS in drinking water for 5 days. Body weight, histological changes, gene expression (qRT-PCR), and protein levels (Western blotting, immunohistochemistry) were evaluated at day 7, day 14, and day 28. No significant differences were observed in inflammation, tissue damage, or repair between Reg(-/-) and WT mice, suggesting that Reg1-3 genes may not be essential in this model or that compensatory mechanisms might mitigate their loss. These findings highlight the need for further investigation into the functional redundancy and context-dependent roles of Reg genes in UC.