The article reviews the dextran sodium sulfate (DSS)-induced model of colitis, a widely used animal model for studying inflammatory bowel disease (IBD). DSS is a sulfated polysaccharide that forms complexes with medium-chain-length fatty acids (MCFAs) in the colonic lumen, leading to the formation of nanovesicles that fuse with colonicocyte membranes and cause inflammation. This model offers several advantages, including reproducibility, ease of generation, and mimicry of critical features of human IBD. However, it is not an exact replica of human colitis, and some results obtained from this model cannot be directly applied to humans. The review discusses the pathogenesis of DSS-induced colitis, including the role of MCFAs, the impact of DSS size and molecular weight, and the involvement of innate immunity and the NLRP3 inflammasome. It also highlights the importance of gut microbiota and genetic factors in the development of colitis. The model has been used to evaluate various therapeutic interventions, both pharmacological and non-pharmacological, and has contributed to the development of treatments for IBD. Despite its limitations, the DSS-induced colitis model remains a valuable tool for advancing our understanding of IBD and identifying potential therapeutics.The article reviews the dextran sodium sulfate (DSS)-induced model of colitis, a widely used animal model for studying inflammatory bowel disease (IBD). DSS is a sulfated polysaccharide that forms complexes with medium-chain-length fatty acids (MCFAs) in the colonic lumen, leading to the formation of nanovesicles that fuse with colonicocyte membranes and cause inflammation. This model offers several advantages, including reproducibility, ease of generation, and mimicry of critical features of human IBD. However, it is not an exact replica of human colitis, and some results obtained from this model cannot be directly applied to humans. The review discusses the pathogenesis of DSS-induced colitis, including the role of MCFAs, the impact of DSS size and molecular weight, and the involvement of innate immunity and the NLRP3 inflammasome. It also highlights the importance of gut microbiota and genetic factors in the development of colitis. The model has been used to evaluate various therapeutic interventions, both pharmacological and non-pharmacological, and has contributed to the development of treatments for IBD. Despite its limitations, the DSS-induced colitis model remains a valuable tool for advancing our understanding of IBD and identifying potential therapeutics.