Abstract: We compared the pharmacokinetic and pharmacodynamic profiles of desmopressin acetate after intraocular, intravenous and intragastric administration in rabbits to better understand the systemic delivery of peptide drugs through intraocular administration. Fifteen rabbits were randomly divided into three groups (intraocular administration, 7 μg·kg^-1; intravenous administration, 0.7 μg·kg^-1; and intragastric administration, 7 μg·kg^-1). Blood samples were taken from the heart at predetermined time points after dosing and the plasma desmopressin concentration was analyzed by enzyme-linked immunosorbent assay (ELISA). Another 21 rabbits were randomly divided into three groups (intraocular administration, 7 μg·kg^-1; intravenous administration, 0.7 μg·kg^-1; intragastric administration, 7 μg·kg^-1) for a pharmacodynamics study. Urine was collected at predetermined intervals after dosing. The pharmacokinetic parameters after intravenous administration were as follows:C_max was 143.0 pg·mL^-1; the area under the plasma concentration-time curve for desmopressin (AUC_0-t) was 999.9 pg·h·mL^-1. The pharmacokinetic parameters after intraocular administration were as follows:t_max was 5 min, C_max was 125.6 pg·mL^-1, AUC_0-t was 873.1 pg·h·mL^-1, and absolute bioavailability (F) was 8.7%. The pharmacokinetic parameters after intragastric administration were as follows:t_max was 10 min, C_max was 104.1 pg·mL^-1, AUC_0-t was 451.8 pg·h·mL^-1, and absolute bioavailability was 4.5%. Intraocular administration and intravenous administration of one tenth of the dosage showed a similar effect, and the urine volume remained decreased for 12 h, but urine volume increased significantly in the second collection period after intragastric administration, and there was no decrease in volume 12 h after dosing. This study demonstrates that peptide drugs such as desmopressin can be absorbed more rapidly after intraocular administration than after intragastric administration and can exert systemic therapeutic effects. In this study, the program of animal testing had been approved by the Laboratory Animal Care and Use Committee at Anhui University of Chinese Medicine.