Abstract: Objective To explore the alterations in the gut microbiota-short-chain fatty acid metabolism axis in a rat model of diarrhea-predominant irritable bowel syndrome (IBS-D), and to explore the effect of sodium butyrate on this axis. Methods Seventeen Wistar rats were divided randomly into three groups. IBS-D was induced by 4% acetic acid enema combined with restraint stress. Sodium butyrate was injected intraperitoneally during the modeling period. The fecal flora was detected by 16S rRNA technology, and the fecal short-chain fatty acid content was detected by liquid chromatography mass spectrometry. Results Rat body weight, the relative abundance of intestinal probiotics, and fecal butyric acid and valeric acid contents were decreased in rats in the model group compared with the normal group, while the abdominal withdrawal reflex score, fecal water content, and relative abundance of Blautia spp. were significantly increased. Treatment with sodium butyrate significantly increased rat body weights and fecal butyric acid and valeric acid contents, and decreased the AWR score, fecal water content, and relative abundance of Blautia spp. , compared with the model group. Conclusions Sodium butyrate can alleviate diarrhea and colon visceral hypersensitivity in IBS-D rats by improving the imbalance in the gut microbiota-short-chain fatty acid metabolic axis.