We investigated the effect of ecabet sodium (ecabet) on rat acute esophageal lesions induced by reflux of gastric juice. Ligation of both pylorus and fore-stomach induced the reflux of gastric juice, decreased the amount of mucus and formed hemorrhagic lesions in the esophageal mucosa. Intragastric injection of ecabet reduced the pepsin activity and prevented both the decrease of mucus amount and formation of lesions. Ecabet enhanced the reduction in lesion formation induced by omeprazole and ranitidine without a change in decreased acid concentration and pepsin activity. Digestion of mucosa and the reduction in mucus were prevented by ecabet in the everted HCl and pepsin treated esophageal sac. These results indicate that ecabet prevents esophageal lesions by inhibiting pepsin activity as well as by protecting mucus from degradation. These further implicate the therapeutic potential of ecabet for prevention/treatment of GERD, especially in combination with a proton pump inhibitor or H(2)-antagonist.