Abstract: Gastrointestinal microorganisms in mammals are part of the bacterial ecosystem and play an important role in gastrointestinal development, function and regulation. Short-chain fatty acids (SCFAs) are metabolites produced by fermentation of beneficial bacteria in gastrointestinal microbiome, mainly including acetate, propionate and butyrate. Currently, most studies focus on the effect of microorganisms on host cell metabolism, but the regulation of short-chain fatty acids on intestinal inflammation and its mechanism is still worthy of attention. More and more studies have shown that SCFAs can provide energy for intestinal epithelial cells, protect the intestinal barrier, regulate intestinal inflammation and other functions. In the treatment of intestinal inflammation, SCFAs can be used as signal molecules to activate G protein-coupled receptors (GPCRs) on the cell surface and inhibit histone deacetylases (HDACs) through substrate transporters in the cell, thus achieving anti-inflammatory goals. In this paper, the composition and source of SCFAs, the synthesis pathway and distribution in the body, the effect on intestinal health, the molecular mechanism of regulation in intestinal inflammation and the effect of dietary fiber on the synthesis of SCFAs are reviewed. The mechanism of short-chain fatty acid regulation of intestinal inflammation is emphasized to provide theoretical basis for further research.