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Background To compare the therapeutic effects of TXNDC5 monoclonal antibody (mAb) with conventional therapeutic agents (prednisolone and sulfasalazine) in a mouse model of dextran sulfate sodium (DSS)-induced inflammatory bowel disease (IBD)-related intestinal fibrosisMethods Forty-eight C57BL/6 mice were randomized into four groups (n=12): Group A (prednisolone, 2 μg/day, ig), Group B (sulfasalazine, 300 μg/day, ig), Group C (TXNDC5 mAb, 10 μg q3d, iv), and Group D (normal saline, ig). Seven mice served as normal controls (Group E). Intestinal fibrosis was induced by four cycles of 2% DSS. After modeling verification (5 mice/group excluded for histology), the remaining mice received a 14-day treatment. Outcomes included body weight, disease activity index (DAI), colon length/weight, serum TGF- β/TNF-α (ELISA), collagen deposition (Masson/Sirius Red staining), and colonic TXNDC5 expression (Western blot/ qPCR). Statistical analysis used one-way ANOVA with Tukey’s post hoc test.Results Group C exhibited the most prominent weight recovery (20.1±1.2%), significantly higher than Groups A (18.7±0.2%) and B (19.4±1.5%), while Group D showed the poorest recovery (3.4±0.9%). Group C achieved DAI=0 on day 11, earlier than Groups A and B (day 13), whereas Group D remained at approximately 1.0. Group C showed the longest colon length (5.17 cm) and lowest colon weight (0.205 g), both significantly better than Groups A, B and D (P<0.05). Serum TGF- β and TNF-α levels, collagen deposition, and TXNDC5 protein and mRNA expression in Group C were the lowest, with significant differences versus Groups A and B (P<0.05). No significant difference was observed between Groups A and B (IDDF2026-ABS-0132 Figure 1, IDDF2026-ABS-0132 Figure 2. Effect of TXNDC5 monoclonal antibody on colonic collagen deposition in mice with DSS-induced intestinal fibrosis).Conclusions TXNDC5 monoclonal antibody exerts significantly superior therapeutic efficacy to prednisolone and sulfasalazine in DSS-induced IBD-related intestinal fibrosis, manifesting as accelerated weight recovery, earlier disease remission, improved colonic morphology, potent anti-inflammatory activity, and marked antifibrotic effects ( IDDF2026-ABS-0132 Figure 3. Schematic diagram of the mechanism underlying the improvement of intestinal fibrosis by TXNDC5 monoclonal antibody).Abstract IDDF2026-ABS-0132 Figure 1Abstract IDDF2026-ABS-0132 Figure 2Abstract IDDF2026-ABS-0132 Figure 3