BACKGROUND:Antibiotic resistance is an emerging public health problem. Centers for Disease Control and Prevention (CDC) has described antibiotic resistance as one of the world's most pressing health problems in 21st century. WHO rated antibiotic resistance as "one of the three greatest threats to human health". One important strategy employed to overcome this resistance is the use of combination of drugs. Many plants, natural extracts have been shown to exhibit synergistic response with standard drugs against microorganisms. The present study focused on the antibacterial potential of propolis in combination with the standard antibiotic Cefixime against the typhoid causing bacteria i.e. Salmonella. METHODS:Ethanolic extract of propolis was taken for the present work. For the experiment BALB/c mice were taken as animal model and divided into ten groups. Along with normal and infected control groups, four different combinations of cefixime and propolis were used. Biochemical, hematological and histopathological indices were studied by following the standard protocols. RESULTS:In BALB/c mice, Salmonella causes severe biochemical, hematological and histopathological alterations by 5th day of infection. Ethanolic extract of propolis at a dose of 300 mg/kg body weight of mice when used alone to treat Salmonella infection in mice gave significant results by 30th day of treatment. Similarly, when cefixime (4 mg/kg body weight of mice) was used to treat infection in mice, significant results as compared to infected control were observed after 5th day. But when propolis and cefixime were used together in different concentrations in combination therapy, evident results were observed after 5 days of treatment. The levels of various liver and kidney function enzymes, blood indices and the histopathology of liver, spleen and kidney were restored to near normal after 5 days of treatment and at much lower doses as compared to the effective dose when used alone. CONCLUSION:The study confirmed that significant results were observed in three combinations of cefixime and propolis as compared to infected controls. Propolis acted synergistically with cefixime and enhanced the efficacy of antibiotic and reduced its effective dose in combined therapy.