PURPOSE: To develop an animal model and investigate the dose-dependent effect of an intraglandular injection of botulinum toxin A (BTX-A) on tear production. METHODS: In a volume of 0.1-ml, 0.625-, 1.25-, or 2.5-U BTX-A was injected transconjunctivally in the superolateral lobe of the lacrimal gland of adult New Zealand white female rabbits. In the contralateral lacrimal gland, 0.1 ml of 0.9% sodium chloride was injected. Prior to injection and at 1-week postinjection, photographs were taken to evaluate pre- and postoperative eyelid position. Fluorescein and Rose Bengal stain were used to evaluate the corneal surface, and Schirmer test was used to assess tear production. RESULTS: Glands injected with the intermediate (1.25 U) and the highest (2.5 U) doses of BTX-A displayed a statistically significant decrease in tear production (p = 0.002 and 0.007, respectively) compared with the contralateral saline-injected glands at 1 week. No corneal pathologic factors from excessive dryness were observed following the injection. While postinjection ptosis was observed (p = 0.025), no difference was seen between BTX-A and saline-injected eyes. CONCLUSIONS: In rabbits, intraglandular injection of BTX-A resulted in decreased tear production at 1 week. No additional reduction in tear production was seen with a BTX-A dose greater than 1.25 U, suggesting glandular receptor saturation at this dose. Despite suppression of tear production, no corneal pathologic factors were observed. Further studies are needed to refine this animal model with the ultimate goal of determining optimum delivery route and concentration to reduction in tear production while minimizing side effects in patients.