<b><i>Purpose:</i></b> A dexamethasone canalicular insert, Dextenza®, has been used to treat anterior inflammation of the eye, including keratoconjunctivitis sicca. This study aimed to investigate the tear pharmacokinetics and systemic exposure of dexamethasone in New Zealand White rabbits after inserting the preparation into the punctum and to correlate the data with the <i>in vitro</i> dissolution test. <b><i>Methods:</i></b> Dextenza was inserted into the punctum of rabbits. A paper strip serially collected tears, and dexamethasone concentrations in tears and plasma were measured using HPLC-MS/MS. The time courses of tear and plasma dexamethasone concentrations were characterized. <b><i>Results:</i></b> The release of dexamethasone from the insert to tears in rabbits was completed in ∼ 5 days, much faster than in humans and dogs (30 days). The time course of plasma dexamethasone concentration was fully characterized, in contrast to the fact that systemic exposure was merely observed in the other species. The present results might be attributed to the anatomical structure of the lacrimal sac beneath rabbits' canaliculi. The <i>in vitro</i> dissolution pattern represented an excellent correlation with the <i>in vivo</i> release in tears. <b><i>Conclusions:</i></b> We first examined the pharmacokinetic study of the canalicular insert in rabbits, which could be applied to the other insert studies in the species.