Non-steroidal anti-inflammatory drugs, essential for the treatment of rheumatic diseases, are frequently associated with significant adverse effects on the integrity of the gastrointestinal mucosa. Sulglicotide (S), a natural product, has been found to possess gastromucosal protective properties. Aim of the present study was to evaluate whether (S) 200 mg t.i.d prevented or reduced the severity of gastric and/or duodenal mucosal injury induced by Diclofenac. A total of 30 patients with either rheumatoid arthritis (RA) or osteoarthritis (OA) who required NSAID therapy for at least 8 weeks were enrolled into a double-blind randomized placebo-controlled study. The main criteria for entry into the trial was the absence of gastrointestinal symptoms, and gastric/duodenal lesions assessed by endoscopy. At the end of the treatment endoscopy and relative symptoms were assessed. Six out of 15 patients, in both groups of treatment developed mucosal injury, but only in the placebo group the gastric damage was important (ulcer and petechiae) while in the group (S) we observed only hyperemia of the gastric mucosa. These preliminary data indicate the usefulness of Sulglicotide in preventing or reducing mucosal injury from NSAID treatment.