A high-performance liquid chromatographic method to determine (Me) Arg-Lys-Pro-Trp-tert-Leu-Leu (NT-2) with neurotensin (NT) activity in rat plasma was developed and a pharmacokinetic study was performed in rats. Quantitative analysis with high reproducibility was achieved for NT-2 over the concentration range of 1.14-500ng/ml.(Me) Arg-Lys-Pro-Trp-tert-Leu-Leu-OEt (NT-1) was rapidly hydrolyzed to NT-2 in rat plasma at 37 C. This degradation of NT-1 was observed as a pseudo first-order reaction, and the pseudo first-order rate constant was calculated to be 7.26 min-1 (t 1/2= 0.095 min). The pharmacokinetic profiles of NT-2 after intravenous administration of NT-1 at doses of 0.1 and 0.3 mg/kg were compatible with that of NT-2 after intravenous administration of NT-2 at 0.5 mg/kg. Range of the half-life of the terminal phase (t 1/2 β) of NT-2 was 0.36-0.53 h. The absolute bioaveilabilities after oral administrations of NT-1 and NT-2 at a dose of 20mg/kg were 0.61±0.17 (mean±SE) and 0.19±0.08%, respectively. It was found that NT-1 was more suitable for oral administration than NT-2.