Zinc is an essential trace mineral that plays a critical role in many biochemical functions, including DNA, RNA, and protein synthesis. Carnosine is a bioactive dipeptide that forms a stable complex with zinc. As an antioxidant, zinc-L-carnosine has a protective effect on the gastric mucosa in in vitro and in vivo rodent models of gastric injury. Aim of this study was to investigate the mucosal protective effects of zinc-L-carnosine in combination with the antioxidant alpha-tocopheryl acetate on the development of aspirin-induced GI lesions in dogs. Eighteen healthy mixed-breed dogs weighing 17 – 24 kg were entered into this randomized double-blinded placebo-controlled study. All dogs were negative for parasites, had normal blood cell counts, serum chemistries, and gastroduodenoscopic exams. On days 0-35, dogs were treated with 1 tablet (n=6) or 2 tablets (n=6) of 30 mg zinc-L-carnosine/ 30 IU vitamin E q12h PO, or a placebo (n=6). On days 7-35, all dogs were given 25 mg/kg buffered aspirin q8h PO for the induction of GI lesions. Endoscopy was performed on days Days -1, 14, 21, and 35, and GI lesions (hemorrhages, erosions, or ulcers) were scored using a 12-point grading scale. Dogs were monitored daily for food intake, vomiting, and diarrhea. Presence of occult fecal blood (Hemoccult SENSA) and body weight were measured once weekly. Blood cell counts and serum chemistries were repeated on Days 14 and 35 for comparison with pre-treatment tests. All dogs tolerated zinc-L-carnosine well without adverse effects. Gastric erosions were seen in all dogs and 17 dogs developed gastric ulcers. In 16 dogs lesions were most severe in the body region of the stomach. The duodenum was less severely affected with a single ulcer in 1 dog and erosions in 7 dogs. We are currently performing comparative analysis of gastroscopy scores by region, time point, and treatment group. Food intake decreased in all dogs; however, body weight was maintained within 1 kg of baseline in all dogs but 2, which had lost 10 and 6.5% of body weight by Day 35. Vomiting occurred in 10 dogs on 1 – 8 out of 35 study days (mean 1.7). Fecal consistency was not affected. The fecal occult blood test was positive in 9 dogs but did not reliably predict GI bleeding. Blood cell counts and serum chemistries showed transient, minor changes in most dogs. One dog developed a mild thrombocytopenia on Day 35. In conclusion, zinc-L-carnosine at 30 or 60 mg dose is well tolerated but did not prevent gastric mucosal lesions in an aspirin-induced gastritis model. The role for zinc-L-carnosine as a gastroprotectant in the clinical setting needs further investigation.