Purpose: The aim of this study was to investigate the antimicrobial and anti-inflammatory properties of an ethanolic extract of propolis, a natural resin produced by honeybees, and to determine synergistic activity between ciprofloxacin and propolis in the treatment of experimental Staphylococcus aureus keratitis. Methods: Sixteen young New Zealand white rabbits were given intrastromal injections of S. aureus strains. Twenty-four hours later, the rabbits were randomly divided into 4 groups: group 1 was treated with topical 0.3% ciprofloxacin drops along with the ethanolic extract of propolis drops; group 2 received topical 0.3% ciprofloxacin drops; group 3 was administered the ethanolic extract of propolis drops, and group 4, the control group, was treated with phosphate-buffered saline (PBS) drops. Drugs were instilled 8 times/day for 72 h. Twenty-four and 96 h after inoculation of bacteria, the eyes were examined by slit lamp to assess corneal opacity. Corneas were removed to count bacteria. Results: Slit lamp examination showed that the corneal opacity scores were significantly lower in eyes that received propolis plus ciprofloxacin than in those treated with ciprofloxacin (p = 0.041) or propolis (p = 0.006) or control eyes treated with PBS (p = 0.0001). There was no significant difference in eyes treated with ciprofloxacin and propolis (p = 1.00). There were significantly fewer bacteria in eyes that received propolis plus ciprofloxacin than in those treated with ciprofloxacin (p = 0.0001) or propolis (p = 0.0001) or control eyes treated with PBS (p = 0.0001). There was no significant difference in eyes treated with ciprofloxacin and propolis (p = 0.38). Conclusions: Taking these findings into consideration, we suggest that the ethanolic extract of propolis has antimicrobial and anti-inflammatory properties for S. aureus keratitis. The combination of ciprofloxacin and propolis had better therapeutic effects than either agent alone. Copyright (C) 2005 S. Karger AG, Basel.