The pharmacokinetics of ketotifen fumarate (KF) was examined after administration in rabbits through four different routes (intravenous, intranasal, oral and rectal). The time-course of the plasma concentration of KF after intravenous administration (1 mg/kg dose) fitted a two-compartment open model. KF was rapidly absorbed and showed a high plasma concentration within 0.33 h after intranasal administration. The absolute bioavailability of KF after intranasal administration was 66%. After oral administration at a dose of 1 mg/kg, the plasma concentration of KF was below the detection limit of HPLC analysis. Even at 5 mg/kg, the value of the area under the plasma concentration-time curve (AUC) after oral administration of KF was significantly lower than that after intranasal administration of 1 mg/kg. Oral bioavailability was only 8%. The very low bioavailability of KF after oral administration might be due to the first-pass effect in the liver. We also prepared suppositories containing KF (1 mg/kg) for rectal administration in rabbits. After rectal administration, KF was rapidly absorbed and its bioavailability was 34%. These results indicated that the intranasal route appears the most effective for administering KF, and that rectal administration may be superior to oral administration in terms of bioavailability.