Diabetes mellitus (DM) continues to be one of the world's most costly and complex metabolic disorders. Accumulating evidence has shown that intestinal dysbiosis and associated inflammation can facilitate the onset and progression of DM. In this work, our goal was to investigate how sodium butyrate (SB) controls the gut microbiota to reduce the intestinal inflammation brought on by diabetes. Male KK-Ay mice were randomized into two groups: the DM model group (intragastric administration of 0.9% normal saline) and the SB treatment group (intragastric administration of 1,000 mg/kg/d SB). The C57BL/6J mice were used as the control group (intragastric administration of 0.9% normal saline). These mice were administered via gavage for 8 weeks. The results revealed that SB-treated mice significantly reduced fasting blood glucose (FBG), body weight, 24 h food and water intake, and improved islet histopathology in DM model mice. SB reduced TNF-α, IL-1β, and iNOS, whereas it enhanced the expression of the anti-inflammatory Arg-1 marker on intestinal macrophages and the secretion of anti-inflammatory IL-10. Specifically, SB was linked to a marked drop in the expression of the Th17 marker RORγt and a substantial increase in the expression of the Treg marker Foxp3. SB treatment was associated with significant reductions in the levels of Th17-derived cytokines such as IL-17 and IL-6, whereas anti-inflammatory Treg-derived cytokines such as TGF-β were increased. Additionally, the analysis results from 16S rDNA sequencing suggested that SB significantly reversed the variations in intestinal flora distribution and decreased the relative abundance of Weissella confusa and Anaerotruncus colihominis DSM 17241 at the species level as well as Leuconostocaceae, Streptococcaceae, and Christensenellaceae at the family, genus, and species levels. These distinct florae may serve as a diagnostic biomarker for DM-induced intestinal inflammation. In addition, the heat map of phylum and OTU level revealed a close relationship between DM-induced intestinal inflammation and intestinal microbiota. The present study suggested that SB may reduce DM-induced intestinal inflammation by regulating the gut microbiota.