The present study was to investigate the effect of glipizide on the pharmacokinetics of losartan in rats. Losartan was administered intravenously (3 mg/kg) and orally (9 mg/kg) in the presence and absence of glipizide (0.3 and 1 mg/kg) to rats. The pharmacokinetic parameters of losartan were significantly altered by the presence of glipizide compared with the control group (given losartan alone). Presence of glipizide significantly (p<0.05, 0.3 mg/kg) increased the area under the plasma concentration-time curve (AUC) of losartan by 48.2% and peak plasma concentration ($C_{max}$) of losartan by 47.4%. Consequently, the absolute bioavailability (AB%) of losartan in the presence of glipizide was 38%, which was enhanced significantly (p<0.05) compared to that in the oral control group (25%). The relative bioavailability (RB%) of losartan increased by 1.18- to 1.48-fold in the presence of glipizide. However, there was no significant change in the peak plasma concentration ($T_{max}$) and terminal half-life ($T_{1/2}$) of losartan in the presence of glipizide. In contrast, glipizide did not affect the pharmacokinetics of intravenous losartan. In conclusion, the presence of glipizide significantly enhanced the oral bioavailability of losartan, implying that glipizide might be mainly to inhibit the cytochrome P450 (CYP) 2C9-mediated metabolism, resulting in reducing gastrointestinal and/or hepatic first-pass metabilism of losartan rather than in reducing P-glycoprotein-mediated efflux and renal elimination of losartan. Concurrent use of glipizide with losartan should require close monitoring for potential drug interactions.