Background <p>Irinotecan, a topoisomerase I inhibitor commonly used to treat advanced colorectal cancer, can cause intestinal mucosal damage and delayed diarrhea, which not only limits its clinical application but also poses significant safety risks to patients.</p> Objectives <p>This study aimed to investigate the therapeutic effects and possible mechanisms of Shubu Wenshen Guchang recipe (SBWGR) on delayed diarrhea caused by irinotecan.</p> Results <p>SBWGR inhibited weight loss and reduced diarrhea scores. It improved histopathological damage to the colon of mice, and reduced the serum levels of LPS and D-LA, and the expression of pro-inflammatory cytokines, and conversely increased the expression of anti-inflammatory cytokines. SBWGR increased the expression of colonic tight junction proteins, decreased the expression of iNOS, increased the expression of CD206, and improved the composition of the gut microbiota. SBWGR reduced the expression of NLRP3 and p-JNK.</p> Conclusion <p>SBWGR can repair the intestinal barrier and inflammatory damage in mice by regulating the gut microbiota and JNK pathway, and finally achieve the effect of treating delayed diarrhea caused by irinotecan.</p> Article highlights <p><UnorderedList Mark="Bullet"> <ItemContent> <p>SBWGR improves intestinal barrier and inflammatory damage in irinotecan induced delayed diarrhea mice;</p> </ItemContent> <ItemContent> <p>SBWGR modulates the JNK signaling pathway in mice with delayed diarrhea;</p> </ItemContent> <ItemContent> <p>SBWGR regulated the composition of gut microbiota in mice with delayed diarrhea.</p> </ItemContent> </UnorderedList></p>