Purpose: To investigate the clinical and microbiological effectivity of intravitreal tigecycline in an experimental rabbit endophthalmitis model caused by imipenem resistant Acinetobacter baumannii. Materials and Methods: Forty-eight eyes of 24 New Zealand white albino rabbits were divided into six groups (n58 in each). The right eyes were divided into three groups and defined as infected group; left eyes were divided into three groups and defined as uninfected group. Infected group received 0.1 ml intravitreal A. baumannii suspension. Twenty-four hours after bacterial inoculation, group 1 received 1 mg/ 0.1 ml tigecycline and group 2 received 0.5 mg/0.1 ml tigecycline. Group 3 eyes received no treatment. In group 4, 0.1 ml of saline solution was injected. Groups 5 and 6 were received intravitreal tigecycline injection of 1 mg/0.1 ml and 0.5 mg/0.1 ml respectively. The eyes were enucleated for histopathological evaluation on the sixth day. Clinical and histological scoring systems were used to evaluate clinical and histological severity of the intraocular infection. Results: The mean clinical scores of the six groups at the sixth day were 11±1.92, 12.4±6.2, 8.5±2.7, 0, 3±1.3, and 3±1.4 respectively. Mean histopathological scores were 7.8±2.8, 7.0±1.5, 5.6±1.4, 0, 0, and 0 respectively. There was no significant difference in mean clinical and histopathological scores of infected group (groups 1, 2 and 3). There was significant difference in mean clinical scores of groups 5 and 6 compared with group 4. Groups 4, 5 and 6 showed normal histological structure in histopathological evaluation and showed no significant difference. Microbiological cure was achieved in all infected eyes. Conclusions: Experimental rabbit endophthalmitis model caused by imipenem resistant A. baumannii was microbiologically cured by intravitreal tigecycline injection. However, a hypersensitivity-like reaction due to intravitreal application of tigecycline limits the use of this antimicrobial agent in A. baumannii endophthalmitis. © 2012 Edizioni Scientifiche per l'Informazione su Farmaci e Terapia.