Objective: Non-steroid anti-inflammatory drugs (NSAIDs) may cause damage in the gastrointestinal system mucosa due to topical harm produced by metabolites as well as a decrease in the hydrophobicity of the stomach mucosa and suppression of prostaglandin synthesis. Protecting the mucosa from these effects means using prophylactic agents. In our study, we aimed to compare the effects of L-glutamine, L-arginine, L-carnitine and ranitidine in preventing these effects among rats whose stomachs were damaged after intake of naproxen and hydrochloric acid (HCl).Material and Methods: The rats included in this study were divided into five groups one of which was the control group and prophylactic agents were administered through the intragastric route to all groups for 10 days (Ranitidine: 50 mg/kg, glutamine: 750 mg/kg, arginine: 300 mg/kg, carnitine: 50 mg/kg). In the second stage 40 mg/kg naproxen sodium followed by 0.5 M HCl (10 cc/kg) were administered to the rats in order to produce damage in the stomach mucosa. After sacrification, stomach materials were examined macroscopically, histologically and histomorphologically. Differences be-tween groups were analyzed using the Mann-Whitney U, Fischer's exact and one-way Anova tests. Statistical significance was set at p = 0.05.Results: Macroscopic examination revealed ulcerous mucosa in 60% and congestion as well as edema in 40% of rats not taking prophylactic agents during the test period. No lesion was present in 22.2% and 20% of the rats taking ranitidine and L-glutamine respectively, a wide-scale ulcer case was not discovered. On the other hand, no statistically significant difference in terms of macroscopic findings were determined between prophylactic agents (p> 0.05). Histological examination did not reveal any lesion in 28% of the rats in the ranitidine group and 4% of the control group (p< 0.05). Furthermore, we could not find any statistical difference between the control and prophylaxis groups in terms of average histomorphological measurements. How-ever, significant differences between ranitidine and arginine groups appeared during histomorphological examinations (p< 0.05).Conclusion: We concluded that histological lesions developed less frequently in rats when they were given prophylactic agents to prevent damage in their stomach mucosa; the least damage in terms of morphological evaluation occurred in the ranitidine group. Further studies on this field, including biochemical mediators are required to accomplish higher rates of treatment in patients who widely depend on the intake of NSAIDs.