The article provides a comprehensive protocol for inducing and evaluating dextran sulfate sodium (DSS)-induced colitis in mice, a widely used model for studying inflammatory bowel diseases (IBD). DSS, a water-soluble sulfated polysaccharide, is administered to mice via drinking water to induce acute or chronic colitis, with the severity and duration of the disease depending on the concentration and duration of DSS exposure. The protocol covers detailed steps for preparing mice, monitoring disease progression, and assessing various aspects of colitis, including body weight, fecal occult blood, histological changes, and molecular markers. Key factors affecting the induction of DSS-induced colitis, such as mouse strain, age, gender, and environmental conditions, are discussed. The article also highlights the importance of the gut microbiota in modulating the severity of DSS-induced colitis and the role of specific cytokines and transcription factors in disease pathogenesis. Overall, the DSS-induced colitis model is valuable for understanding the complex mechanisms of IBD and testing potential therapeutic interventions.The article provides a comprehensive protocol for inducing and evaluating dextran sulfate sodium (DSS)-induced colitis in mice, a widely used model for studying inflammatory bowel diseases (IBD). DSS, a water-soluble sulfated polysaccharide, is administered to mice via drinking water to induce acute or chronic colitis, with the severity and duration of the disease depending on the concentration and duration of DSS exposure. The protocol covers detailed steps for preparing mice, monitoring disease progression, and assessing various aspects of colitis, including body weight, fecal occult blood, histological changes, and molecular markers. Key factors affecting the induction of DSS-induced colitis, such as mouse strain, age, gender, and environmental conditions, are discussed. The article also highlights the importance of the gut microbiota in modulating the severity of DSS-induced colitis and the role of specific cytokines and transcription factors in disease pathogenesis. Overall, the DSS-induced colitis model is valuable for understanding the complex mechanisms of IBD and testing potential therapeutic interventions.