BACKGROUND: Helicobacter pylori (H. pylori) has been introduced by since 1983 by Marshal and Warren to play the main role in the pathophysiology of gastritis and gastric ulcers. Almost half of the world population1 is infected by H. pylori. Current therapeutic regimen against H. pylori includes the use of a proton pump inhibitor plus two or more antibiotics. However, the efficacy of this regimen is decreasing mainly due to antibiotic resistance and side effects of medications. This fact has resulted in public interest in other therapeutic options and the role of probiotics merits special attention in this regard. OBJECTIVE: This study aims to evaluate the efficacy of honey-derived Lactobacillus rhamnosus on H. pylori-induced gastric inflammation and gastro-intestinal infection in C57BL/6 Mice. METHODS: The 24 C57BL/6 Mice were randomly divided into three groups of eight mice each. All the mice were fed with 1cc suspension containing 5*1010 CFU/ mL of ATCC43504 strains of H. pylori for 3 consecutive days, twice daily via polyethylene gavage tubes. At the end of 4th week, infection with H. pylori was confirmed with stool Ag (ELISA) and following sacrifice of one mouse from each group, histopathologic study confirmed gastritis. The groups were subjected to different therapies as stated, 1: without Bismuth (Bi), Omeprazole (Om) and L. rhamnosus prescription, 2: Bi, Om and Clarithromycin (Cl) and 3: Bi, Om plus 1cc of suspension of 109 CFU/mL of L. rhamnosus. After 2 weeks, the stool was analyzed for Ag and the mice were sacrificed for evaluation of histopathologic changes. RESULTS: Treatment with L. rhamnosus group provided Zero titer of stool Ag and was associated with improved gastric inflammation in all subjects, similar to the clarithromycin group. CONCLUSION: Honey-derived L. rhamnosus probiotics provides similar results as clarithromycin in terms of improvement of H. pylori infection and gastritis in C57BL/6 Mice model, without its cons of antibiotic resistance.