Purpose: To investigate the efficacy of intravitreal piperacillin/tazobactam (250 mug/0.1 ml) In the treatment of experimental Pseudomonas aeruginosa endophthalmitis in rabbits. Materials and Methods: Twenty New Zealand White albino rabbits were used in this study. The rabbits Department of Ophthalmology, were divided into two groups (10 rabbits in each), and the right eyes were treated with 0.1 ml intravitreal injections of P. aeruginosa suspension (ATCC 27853, 2 x 10(4) CFU); the left eyes served as uninfected control and were injected with 0.1 ml of saline solution. The right eyes of rabbits in group 1 (n = 10) received intravitreal Injection of 250 mug piperacillin/tazobactam 24 h after intravitreal inoculation of P. aeruginosa. Group 2 eyes (n = 10) received no treatment and served as infected controls. Clinical examination of the eyes in each group was performed on the first, third, and sixth day after the inoculation of P. aeruginosa. After the last ophthalmic examination, 0.1 ml vitreous aspirates were obtained for microbiological analysis, and then the eyes were enucleated for histopathological evaluation. Results: The mean clinical scores of group I and group 2 at the first day after P. aeruginosa inoculation were similar (p > 0.05). At the sixth day, the mean clinical score of group I was significantly lower when compared with group 2 eyes (p < 0.001). Microbiological analysis revealed that group 2 had a significantly more cfu/ml than group 1 (p < 0. 001), and the mean histopathological score of group 2 was significantly higher than group 2 (p = 0.009). Conclusions: Intravitreal application of 250 mug/0.1 ml piperacillin/tazobactarn seems to be effective in the treatment of P. aeruginosa enclophthalmitis in rabbits. Intravitreal piperacillin/tazobactarn combination may be a new therapy for P. aeruginosa enclophthalmitis.