The aim of this study was to investigate whether a periocular capsular drug delivery system (DDS) can release dexamethasone sodium phosphate (DEXP) in vitro and in vivo to the posterior segment of rabbit's eye. In vitro, the periocular capsular DDS containing 2 mg/ml or 5 mg/ml DEXP was immersed in modified Franz diffusion cell. Four-hundred microliters of liquid was aspirated at 0.5, 1, 2, 4, 8, 24 and 48 h for determination. In vivo, the DEXP-filled periocular capsular DDS was implanted into the sub-Tenon's sac of the New Zealand rabbit. DEXP concentration at the serum aqueous humor, cornea, iris, lens, ciliary body, vitreous, retina, choroids and sclera was quantified at 1, 3, 7, 14, 28 and 56 d after implantation. The DEXP concentration was determined by ultra-performance liquid chromatography-tandem mass spectrometry. In vitro, the periocular capsular DDS released the DEXP in time-dependent manner from 1/2 to 48 h. In vivo, the concentrations of the DEXP at the retina, choroids, ciliary body and iris were 123.11 (91.23, 732.61) ng/g, 362.46 ± 330.46 ng/g, 71.64 (71.35, 180.21) ng/g and 192.50 ± 42.66 ng/g, respectively, at 56 d after implantation. Minimal DEXP was found in the aqueous, serum and vitreous. Our results demonstrated that DEXP could be sustained released from the periocular capsular DDS, which indicated that the periocular capsular DDS might be a potential candidate of transscleral drug delivery for the management of posterior segment diseases.