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Recent findings indicate that in addition to its hyperlipemic effect, a high fructose diet has a pro-oxidant effect in rats compared with a starch-based diet. Oligofructose (OFS) has already been shown to decrease plasma lipids in rats. We assessed the impact of fructose on oxidative stress by supplementing a high fructose diet with OFS. Rats were fed either a high fructose diet or a starch-based diet, with or without supplementation of 10 g/100 g oligofructose for 4 wk. Regardless of the type of carbohydrate, OFS in the diet produced an enlargement of the cecum and led to a significant increase in the SCFA cecum pool. Fructose feeding was associated with significantly higher insulin plasma concentrations (+63%) in the control groups, whereas insulin plasma concentrations did not differ in rats fed the fructose diet supplemented with OFS. Plasma leptin concentration was significantly lower (approximately 50%) in the OFS-supplemented fructose group compared with the other three groups. Fructose feeding in rats also significantly increased plasma (P < 0.001) and liver (P < 0.001) triglyceride (TG) concentrations and the addition of OFS prevented the TG accumulation induced by fructose in the liver (P < 0.05) and hyperlipemia (P < 0.05). OFS consumption prevented (P < 0.05) the lower plasma vitamin E/TG ratio in rats fed the fructose diet. Control rats fed the fructose diet had high plasma TBARS values compared with rats fed the starch diet, whereas TBARS values remained unchanged when rats were supplemented with OFS. Control rats fed the fructose diet had higher TBARS urine values and higher heart tissue susceptibility to peroxidation compared with rats fed the starch diet, and this effect was significantly reduced by OFS consumption. Further studies are required to identify the mechanisms underlying the protective effect of OFS against the pro-oxidant effect of fructose. However, the potential nutritional benefits of OFS supplementation in fructose-rich diets are suggested.