PGC-1α expression is a tissue-specific regulatory feature that is extremely relevant to diabetes. Several studies have shown that PGC-1α activity is atypically activated in the liver of diabetic rodents and contributes to hepatic glucose production. PGC-1α and Foxo1 can physically interact with one another and represent an important signal transduction pathway that governs the synthesis of glucose in the liver. However, the effect of physical activity on PGC-1α/Foxo1 association is unknown. Here we investigate the expression of PGC-1α and the association of PGC-1α/Foxo1 in the liver of diet-induced obese rats after acute exercise. Wistar rats swam for two 3 h-long bouts, separated by a 45 min rest period. Eight hours after the acute exercise protocol, the rats were submitted to an insulin tolerance test (ITT) and biochemical and molecular analysis. Results demonstrate that acute exercise improved insulin signalling, increasing insulin-stimulated Akt and Foxo1 phosphorylation and decreasing PGC-1α expression and PGC-1α/Foxo1 interaction in the liver of diet-induced obesity rats under fasting conditions. These phenomena are accompanied by a reduction in the expression of gluconeogenesis genes, such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphate (G6Pase). Thus, these results provide new insights into the mechanism by which exercise could improve fasting hyperglycaemia. © 2009 The Authors. 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