Francolins ophthalmia is often caused by resistant conditional pathogenic bacteria. Conditional pathogenic Staphylococcus saprophyticus is a potential reservoir of macrolides antibiotics resistance gene. Baicalin has been reported as a potential agent to synergistically inhibit the replication of Staphylococcus. The objective of this study was to isolate the pathogen of the francolins ophthalmia, identify the antibiotic resistance profile of isolated S. saprophyticus, and investigate the effect of baicalin combined with azithromycin (Azm) against azithromycin resistant S. saprophyticus (ARSS). The ARSS was isolated and identified from francolins suffered from ophthalmia by phenotypic and molecular biology methods. The antibiotic resistance profile was identified by Kirby-Bauer method. Then the minimal inhibitory concentration (MIC) of Azm in absence and presence of a sub-inhibitory concentration baicalin/verapamil was determined to assess the effect that baicalin combined with Azm against ARSS. ARSS was isolated and identified from francolins experienced ophthalmia. The isolated ARSS was resistant to 11 among the 13 antibiotics that were tested. The synergistic effect of baicalin and Azm was noticed with a reduction rate varied from 2 to 128-fold. It appears from this study that S. saprophyticus can cause francolins ophthalmia and baicalin may be used as a natural agent resistance inhibitor for ARSS.