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Gegen Qinlian Decoction (GQD) is a commonly used traditional Chinese medicine formula for treating type 2 diabetes mellitus and insulin resistance (IR). The effects of GQD treatment on intestinal flora and its metabolism, however, are yet to be understood. In this study, the effects of GQD treatment on the fecal metabonome of high fructose-induced IR rats were investigated with a 1H NMR-based approach. The IR model was established by feeding the rats with 10% fructose solution for 8 consecutive weeks. The animals in the GQD treatment group were gavaged with GQD daily (18.2 g/kg/day) from the 5th to 8th week. Compared with control group, The IR rats showed significantly increases in water/food intakes, body weight and IR index at the ends of the 4th and 8th week. The fasted plasma glucose (FPG) level of the IR rats increased by the end of the 8th week. The GQD treatment lowered the IR index and normalized fecal metabonome by increasing the levels of propionate, acetate, succinate, taurine and glycerol, while decreasing the levels of n-butyrate, alanine and glutamate. These results indicated that the GQD treatment induced positive changes in amino acid metabolism, fatty acid oxidation and gut microbiota metabolism in the IR rats.