Abstract: The pharmacodynamics of prostaglandin E₁ (PGE₁) administered by different routes to rats was investigated in this paper. The hypotensive effect of PGE₁ was used as an index of drug efficacy, pharmacodynamic parameters such as time to reach peak effect (T_max), maximal percentage of blood pressure decrease (E_max, %), duration of effect (T_d), and the area under the blood pressure decrease percent-time curves (AUC, %·min) were determined after PGE₁ given to rats intranasally, sublingually, intraperitoneally (ip),and intramuscularly (im), separately, and compared with those obtained from intravenous (iv) administration. Similar to iv route, the pharmacodynamic parameters of PGE₁ from the other administration routes, E_max, T_d and in particular AUC values were all increased with increasing doses, showing dose-efficacy relationship. T_max was found to be approximately 3-4 min for nasal route, 3-8 min for im, 6-8 min for ip and 12-30 min for sublingual route, separately. Thus, the order of magnitude of absorption rate of the drug was as follows: nasal≈im>ip>sublingual. If the pharmacological bioavailability (PF) for each administration route was used as a tentative measure of drug absorption extent, the order of magnitude of absolute bioavailability appeared as follows: nasal>im≈ip>sublingual. Furthermore, the interindividual difference was found to be larger for im and ip route than that for nasal and sublingual route. These results indicate nasal and sublingual routes are two promising routes for the systemic delivery of PGE₁ in clinical applications.