The use of intravitreal steroids to treat bacterial endophthalmitis remains controversial. The efficacy of intravitreal vancomycin alone (group 1), intravitreal dexamethasone alone (group 2), and a combination of intravitreal vancomycin and dexamethasone (group 3) in the treatment of experimental methicillin-resistant Staphylococcus epidermidis endophthalmitis was evaluated in a rabbit model: 24 h after bacterial inoculation of all eyes, right eyes were treated and left eyes served as infected controls. Vitreal aspirations and grading of vitreal inflammatory reaction were done regularly until sacrifice. Group 2 eyes demonstrated more inflammation histologically than control eyes. Vitreal aspirations demonstrated no growth by 5 days from groups 1 and 3 eyes. Although the clinical appearance was not significantly different between groups 1 and 3, the histologic appearance of group 3 eyes showed less intense intraocular inflammation. Treatment with dexamethasone in the absence of appropriate antibiotics was more harmful than no treatment at all (P < .05). Therapy with both intravitreal vancomycin and dexamethasone results in less inflammation than intravitreal vancomycin alone in this model.