Staphylococcus epidermidis is one of the most common causes of postoperative infectious endophthalmitis, which is a serious complication of ocular surgery and penetrating trauma. Moxifloxacin is a newly developed fluoroquinolone with a potent antimicrobial activity. Corticosteroids are used in endophthalmitis to suppress devastating intraocular inflammatory response. This study was designed to assess the efficacy of intravitreal moxifloxacin alone and in combination with intravitreal dexamethasone. To the best of our knowledge, there is no published report demonstrating the effect of intravitreal moxifloxacin on bacterial endophthalmitis. One eye of each rabbit (n = 24) was infected by inoculation of 10⁵ colony-forming units (CFU) of S. epidermidis into the vitreus cavity. Rabbits received intravitreal injection of moxifloxacin (50 μg) or a combination of moxifloxacin (50 μg) and dexamethasone (400 μg). No treatment was given to control group. Clinical and histopathological examination scores and microbiological analysis of vitreus aspirates were compared. In the treatment groups, the clinical and histopathological scores and mean CFU were significantly lower than those in the control group (p < 0.05) but showed no significant difference between the treatment groups. These results suggest that intravitreal injection of moxifloxacin is effective against S. epidermidis in this experimental rabbit model. Moxifloxacin may be a promising agent in the treatment of bacterial endophthalmitis.