To investigate the histological and anatomical characteristics of the lacrimal duct system (LDS) in rabbits and rats and compare with that in humans to establish a suitable animal for LDS studies.

New Zealand white rabbits (1.8–2 kg) and SD rats (250–300 g) were selected. Following tests were executed on their LDS, including anatomical measurements; computed tomographic dacryocystography; hematoxylin and eosin, Masson’s trichrome, Periodic Acid-Schiff staining, and scanning electron microscope.

Although there were anatomical similarities between the rats and humans in LDS, the size of LDS was too small and the epithelial types differed from that of humans in LDS. The rabbit only had a lower lacrimal punctum and a lacrimal canaliculus, while they had the same types of lacrimal epithelium as human’s and the size was suitable for clinical probing and intubation.

Histologically, the lacrimal canaliculi of both rabbits and rats resemble those of humans, making both species applicable for biological studies targeting the lacrimal canaliculi. Nevertheless, the epithelial types of the lacrimal sac and nasolacrimal duct in rats differ significantly from humans, whereas those in rabbits are consistent with humans. Therefore, rabbits are more appropriate for biological research involving the nasolacrimal duct and lacrimal sac.