Introduction: The consumption of high fat and high fructose (HFHF) diet promotes an increase in free fatty acids (FFA) circulating in adipose, muscle and liver tissues, causing an increase in adipogenesis that results in the accumulation of visceral fat, insulin resistance, inflammation and impairment of lipid metabolism, as well as an increase in fatty deposits in the liver that results in liver steatosis. In this sense, sorghum BRS 305 stands out for being a cereal with bioactive compounds that can help prevent obesity and hepatic steatosis with the ability to modulate the composition of the intestinal microbiota, reducing the problems generated by the diet in addition to being a low-cost, easy-to-produce, gluten-free. Objective: The aim of the study was evaluate the effect of sorghum flour on insulin resistance, glucose tolerance, adiposity, hepatic steatosis, microbiota modulation, inflammation and oxidative stress in Wistar rats fed a high-fat high-fructose diet. Methodology: The study was divided into two phases. In the first phase male Wistar rats (n=30) at 40 days of age, were allocated into two groups: control AIN93-M (normal control: n=10) and high-fat and high-fructose (HFHF) (30% pork fat and 20% of fructose) (n=20) for 7 weeks to induce metabolic changes. In the second phase, the control AIN93-M manteined with the same diet, and the HFHF group were divided into two groups: HFHF (HFHF control: n=10) and HFHF + sorghum flour (replacing 50% dietary fiber, 100% starch, 19.8% protein and 22.5% lipids in the experimental diet), (n=10), for 10 weeks. At the end of the period, the animals were euthanized. Blood, liver, feces, colon and adipose tissues were collected to evaluate biochemical and inflammatory markers, intestinal microbiota and antioxidant capacity. Data will be submitted to ANOVA followed by the Newman-Keuls test (α=0.05) performed in the GraphPadPrism software, version 7.0. Microbiota data were corrected for multiple comparisons using false discovery rate (FDR) in the STAMP software. Results: Article 1: The consumption of sorghum flour reduced adiposity, as well as the levels of triglycerides, uric acid, alanine aminotransferase, hepatic steatosis and lipogenesis. In addition, sorghum improves glucose metabolism by act directly on insulin sensitivity and glucose tolerance and increased the concentration of PPARα protein in the liver. Article 2: Sorghum flour decreased the concentration of nitric oxide, phosphoprotein kinase B (Akt), nuclear factor-kappa B (p65-NFκB), toll-like receptor 4 (TLR4) and lipid peroxidation in the liver. In addition, sorghum flour improved superoxide dismutase and catalase activities and total plasma antioxidant capacity. Article 3: The intake of the whole sorghum flour showed higher relative abundance of Firmicutes and higher Firmicutes/Bacteroidetes ratio in relation to the other experimental groups, and lower abundance of Bacteroidetes when compared to the HFHF group. Despite this, sorghum increased the production of short- chain fatty acid (SCFA) as propionate and the circular muscle layer, as well as the abundance of the genera Roseburia and Lachnospiraceae_NK4A136_group in relation to the HFHF group. Conclusion: Consumption of sorghum BRS 305 with high content of tannin and resistant starch improved inflammation and oxidative stress by inhibiting the activation of NFκB-p65; further modulated adiposity and glucose metabolism, reducing liver steatosis and lipogenesis. Finally, the consumption of the HFHF diet associated with sorghum flour modulated the composition of the intestinal microbiota and the abundance of SCFA-producing bacteria. Keywords: Adiposity. Metabolic change. Resistant starch. Tannins. Glucose tolerance. Intestinal microbiome. Free fatty acids. Intestinal homeostasis. Short-chain fatty acids.