Chlorogenic acid (CGA), an abundant polyphenol compound in plants, exhibits anti-oxidant effects. The protective effect of CGA in the rat intestine with endotoxin infusion was evaluated. CGA administration ameliorated endotoxin-induced intestinal injury, and decreased the ratio of lactulose/mannitol, the ileum pathological grade, the myeloperoxidase activity in the ileum, and the malondialdehyde content in the ileum and in ileum mitochondria. The small intestine weight, activities of alkaline phosphatase and superoxide dismutase in the ileum, and β-nicotinamide adenine dinucleotide reduce form (NADH) dehydrogenase and succinate dehydrogenase activities in ileum mitochondria were increased. Intestinal permeability was positively correlated with intestinal mitochondrial injury indicated as the level of malondialdehyde in ileum mitochondria, and negatively correlated with NADH dehydrogenase activity. Dietary administration of CGA protected against increased intestinal permeability caused by endotoxin infusion. The protective effect of CGA was probably associated with a decrease in mitochondrial lipid peroxidation levels and an increase in NADH dehydrogenase activity.