The aim of this study was to test the hypothesis that non-digestible fructans, namely oligofructose (OFS), are able to decrease post-prandial lipaemia in rats fed a high-fat diet composed of 10% lard, 4% corn oil and 0.15% cholesterol. Male Wistar rats were divided into three groups: group 1 was fed a standard low-fat diet (AO4), group 2 received the high-fat diet (HF) and group 3 received 10% (w/w) OFS in the HF diet (HF-OFS) for 3 weeks. The OFS supplementation reduced post-prandial triglyceridaemia by more than 50%, compared to both AO4 and HF groups. It also protected rats against the increase in free cholesterol serum level induced by the HF diet. The OFS did not prevent the HF-induced hepatic accumulation of triglycerides, phospholipids and cholesterol; however, histochemical analysis showed smaller lipid droplets in the liver of HF-OFS rats as compared to HF rats. Our results suggest that, when given in HF diet, OFS decreases serum triglycerides through an extra-hepatic event, namely by enhancing triglyceride-rich lipoprotein catabolism.