The present study investigated the effects of hydrocortisone on the pharmacokinetics of loratadine in rats after intravenous and oral administration. A single dose of loratadine was administered either orally (4 mg/kg) or intravenously (1 mg/kg) with or without oral hydrocortisone (0.3 or 1.0 mg/kg). Compared to the control group (without hydrocortisone), after oral administration of loratadine, the area under the plasma concentration-time curve (AUC) was significantly increased by 30.2-81.7% in the presence of hydrocortisone (p<0.05). The peak plasma concentration ($C_{max}$) was significantly increased by 68.4% in the presence of 1.0 mg/kg hydrocortisone after oral administration of loratadine (p<0.05). Hydrocortisone (1.0 mg/kg) significantly increased the terminal plasma half-life ($t_{1/2}$) of loratadine by 20.8% (p<0.05). Consequently, the relative bioavailability of loratadine was increased by 1.30- to 1.82-fold. In contrast, oral hydrocortisone had no effects on any pharmacokinetic parameters of loratadine given intravenously. This suggests that hydrocortisone may improve the oral bioavailability of loratadine by reducing first-pass metabolism of loratadine, most likely mediated by P-gp and/or CYP3A4 in the intestine and/or liver. In conclusion, hydrocortisone significantly enhanced the bioavailability of orally administered loratadine in rats, which may have been due to inhibition of both CYP 3A4-mediated metabolism and P-gp in the intestine and/or liver by the presence of hydrocortisone.