Objective:Endocarditis is a rare but serious infection caused byListeria monocytogenes.Panax ginsengdemonstrated multiple immunomodulatory effects in earlier studies. Ampicillin is known as an effective antibiotic in the treatment of this disease. Therefore, this study aimed to evaluate the effect of hydro-alcoholic extract ofP. ginsengand ampicillin treatment in an animal model ofListeria monocytogenes-induced endocarditis.Materials and Methods:Thirty mice, 5-7 weeks old, were randomly divided into five groups (n=6) including Healthy Control, Infected, Ampicillin (20 mg/kg, subcutaneous) treatment, Ginseng (0.025 mg/kg, intraperitoneal) treatment, and Ginseng (0.025 mg/kg, intraperitoneal) +Ampicillin (15 mg/kg, subcutaneous) treatment groups. The concentration of cytokines in heart tissue, such as IL-1 (interleukine-1), IL-6, IL-8, and TNF-α (Tumor Necrosis Factor-α), was measured. Histopathological changes were evaluated in heart tissues.Results:The levels of cytokines were significantly decreased in the Ampicillin+Ginseng treated group compared to the other experimental groups. Microscopically, pathologic changes in heart tissue were concomitant with biochemical findings, which in the infected group, neutrophils and mononuclear cells infiltration in endocardial tissue, myocardial cell necrosis, and edema were detectable. The Ampicillin+Ginseng group showed no significant changes compared to the normal control group.Conclusion:This study showed that ginseng hydro-alcoholic extract plus ampicillin has better efficacy than the extract or antibiotic alone against experimental endocarditis caused by Listeriosis.