Bacterial infections are becoming increasinglydifficult to treat due to the increasing number of multidrugresistantstrains. Cathelicidin-BF (BF-30) is a cathelicidinlikeantimicrobial peptide and exhibits broad antimicrobialactivity against bacteria. In the present study, the antibacterialactivity of BF-30 against ciprofloxacin-resistantEscherichia coli and Staphylococcus aureus was examined,and the protective effects of this peptide against these bacteriain rats with bacterial vaginosis were identified for thefirst time. The data showed that BF-30 had effective antimicrobialactivities against ciprofloxacin-resistant E. coliand S. aureus. The minimal inhibitory concentrations forboth bacterial strains were 16 lg/ml, and the minimal bactericidalconcentrations were 64 and 128 lg/ml, respectively. A time course experiment showed that the CFUcounts rapidly decreased after BF-30 treatment, and thebacteria were nearly eliminated within 4 h. BF-30 couldreduce the fold change (CFU/ml) in local colonization bydrug-resistant E. coli and S. aureus to 0.01 at a dose of0.8 mg/kg/day in the rats’ vaginal secretions. In addition,BF-30 induced membrane permeabilization and bound to thegenomic DNA, interrupting protein synthesis. Taken together,our data demonstrate that BF-30 has potential therapeuticvalue for the prevention and treatment of bacterialvaginosis.