Abstract The efficacy of systemic antibiotics in the treatment of granulating wounds has been evaluated. A reproducible laboratory animal model on a chronic granulating wound has been developed and used to evaluate the ability of systemically administered antibiotics to decrease the bacterial flora in the wound. No significant reduction in bacteria was found. This appears to be due to the absence of the antibiotic in the granulation tissue. It is suggested that the fibrin base of a granulating wound may prevent adequate antibiotic penetration into the wound. From this study, therefore, it is suggested that systemic antibiotics have no role in attempting to decrease the bacterial count in a granulating wound.