Background: To investigate the highest nontoxic intravitreal dose of piperacillin/tazobactam in rabbits. Material and Methods: Forty New Zealand white albino rabbits were used in this study. The rabbits were divided into four equal groups ( 10 rabbits in each) and the right eyes were treated with 0.1 ml intravitreal injections of 1,000 mug piperacillin/tazobactam in group 1, 500 mug in group 2, 250 mug in group 3, and 100 mug in group 4. The left eyes served as controls and were injected with 0.1 ml of saline solution. Ganzfeld electroretinogram ( ERG) was performed on all eyes before and after 4 weeks of intravitreal injections. Then, the rabbits were killed and the eyes were enucleated for histopathological evaluation of the retina. Retinal sections were evaluated by morphometric analyses on cell counts of ganglion cell layer and thickness of the various retinal layers. Results: Baseline ERGs were similar among the groups (p > 0.05). After 4 weeks of injection, there were a reduction of the b-wave amplitude and extension of the b-wave implicit time in photopic and scotopic ERGs in group 1 and group 2 when compared with controls (for each, p < 0.001). Intravitreal injection of 100 and 250 mu g piperacillin/tazobactam did not cause any deterioration of the b-wave of ERGs throughout the follow-up period of 4 weeks ( for each, p > 0.05). After morphometric analysis of retinal sections in all groups, there were no statistically significant differences in the mean number of surviving ganglion cells, thickness of the whole retina and the inner plexiform layer compared with controls (p > 0.05). Conclusion: 250 mug/0.1 ml piperacillin/tazobactam is the highest nontoxic dose to the normal retinas of adult albino rabbits as intravitreal injection. Piperacillin/tazobactam may be a new, potentially important drug in the treatment of endophthalmitis as it has a broad antimicrobial spectrum. Copyright (C) 2004 S. Karger AG, Basel.