Dextran sulfate sodium (DSS)-induced colitis is a widely used mouse model for studying inflammatory bowel disease (IBD). This model is simple, reproducible, and closely resembles human ulcerative colitis. DSS, a negatively charged sulfated polysaccharide, induces colitis when administered in drinking water. The severity of colitis depends on DSS concentration, molecular weight, and mouse strain. The model allows for the study of both acute and chronic colitis, as well as the role of the innate immune system and gut microbiota in disease development. Key factors influencing the model include DSS source, molecular weight, mouse strain, and environmental conditions. The protocol describes the induction of DSS-induced colitis, monitoring disease activity, and analyzing tissue samples for inflammation markers. The model is useful for evaluating therapeutic interventions and understanding the mechanisms of IBD. Despite its advantages, the model has limitations, such as the absence of T and B cells in colitis development. The model is also influenced by the gut microbiota, which is essential for robust colitis. The protocol includes detailed steps for DSS administration, monitoring, and analysis of disease progression. The model is widely used in IBD research due to its simplicity, reproducibility, and ability to mimic human disease. The model has been instrumental in understanding the role of the immune system, microbiota, and environmental factors in IBD pathogenesis. The protocol provides a comprehensive guide for researchers to induce and evaluate DSS-induced colitis in mice.Dextran sulfate sodium (DSS)-induced colitis is a widely used mouse model for studying inflammatory bowel disease (IBD). This model is simple, reproducible, and closely resembles human ulcerative colitis. DSS, a negatively charged sulfated polysaccharide, induces colitis when administered in drinking water. The severity of colitis depends on DSS concentration, molecular weight, and mouse strain. The model allows for the study of both acute and chronic colitis, as well as the role of the innate immune system and gut microbiota in disease development. Key factors influencing the model include DSS source, molecular weight, mouse strain, and environmental conditions. The protocol describes the induction of DSS-induced colitis, monitoring disease activity, and analyzing tissue samples for inflammation markers. The model is useful for evaluating therapeutic interventions and understanding the mechanisms of IBD. Despite its advantages, the model has limitations, such as the absence of T and B cells in colitis development. The model is also influenced by the gut microbiota, which is essential for robust colitis. The protocol includes detailed steps for DSS administration, monitoring, and analysis of disease progression. The model is widely used in IBD research due to its simplicity, reproducibility, and ability to mimic human disease. The model has been instrumental in understanding the role of the immune system, microbiota, and environmental factors in IBD pathogenesis. The protocol provides a comprehensive guide for researchers to induce and evaluate DSS-induced colitis in mice.