Background: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most significant human pathogens that cause both nosocomial and community-acquired infections worldwide which are associated with high morbidity and mortality rates with rapid development of resistance. Honey is one of the oldest traditional medicines considered to be important in the treatment of several human ailments including infections not responding to standard antiseptic and antibiotic therapy. Assessing the antimicrobial effect of honey on antibiotic resistant bacteria has a paramount importance. Objective: To assess in vitro antimicrobial effect of Ethiopian multi-flora honey against MRSA. Methods: The antimicrobial effect of Ethiopian multi-flora honey against MRSA was investigated by a tube dilution method for determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). A MRSA isolate was inoculated on nutrient broth medium containing various concentrations of honey solutions and incubated aerobically at 36-37oC. After overnight incubation the tubes were read macroscopically to confer the growth by comparing with that of the control tubes and were sub cultured on agar plate to determine the lowest concentration of the test honey that prevent any visible growth represents the MIC. The MBC could also be determined at the lowest concentration of honey that can kill 99.9% of the bacteria. Result: The mean MICs and MBCs were 11.25 % (v/v) and 16.25 % (v/v) for the __ampersandsignldquo;Tazma mar__ampersandsignrdquo; from low land , 9.38 and 14.38 % (v/v) __ampersandsignldquo;Tazma mar__ampersandsignrdquo; from high land , 23.12 and 28.12 % (v/v) red honey from low land, 33.12 and 38.12 % (v/v) red honey from high land, and 17.5 and 22.5% (v/v) white honey from high land areas respectively against MRSA. Conclusion: Honey has both a bacteriostatic and bactericidal activity. However, the __ampersandsignldquo;Tazma mar__ampersandsignrdquo; honey antibacterial potency on both the test (MRSA) and control bacterial isolates was highly effective than other honey types.