BACKGROUND The intestine is increasingly recognized as a primary effector of distant organ damage, such as the lung, after any abdominal surgery. Earlier studies have shown that surgical manipulation of the intestine induces generation of reactive oxygen species in the intestine, resulting in mucosal and lung damage. Because glutamine is preferentially used by the small intestine as an energy source, this study examined the effect of glutamine and glutamic acid on intestinal and lung damage after surgical manipulation. METHODS Controls and rats were pretreated for 7 days with 2% glutamine or glutamic acid, or the isonitrogenous amino acids glycine or alanine in the diet and subjected to surgical manipulation of the intestine. The intestine and lung were assessed for damage, and protection offered by various amino acids was studied. RESULTS Surgical manipulation resulted in oxidative stress in the intestine as evidenced by increased xanthine oxidase activity and decreased antioxidant status. Enterocyte mitochondria were also functionally impaired with altered calcium flux, decreased respiratory control ratio, and increased swelling. Gut manipulation also resulted in neutrophil infiltration and oxidative stress in the lung as assessed by an increase in myeloperoxidase activity, lipid peroxidation, and antioxidant status. Glutamine or glutamic acid supplementation for 7 days before surgical manipulation showed a protective effect against the intestinal and lung damage. CONCLUSIONS This study suggests that preoperative enteral glutamine or glutamic acid supplementation attenuates intestinal and lung damage in rats during surgical manipulation and that this effect might offer protection from postsurgical complications.