Diltiazem (DTZ) 20 mg/kg was given to male Sprague-Dawley rats either orally (p.o.) or intra-arterially (i.a.) over a 5 min period (n = 6 for each group). Plasma concentrations of DTZ and its major basic metabolites were determined by high performance liquid chromatography assay (HPLC) as previously described over a 10 h period. The major metabolites found in the rat plasma were M2, followed by M6, MA, M1, and then M4. The metabolite Mx was measurable only in some of the plasma samples, and MB was not detected in this species. The mean apparent half-life (t1/2) of the measurable metabolites were longer than the parent DTZ. The metabolism profiles were qualitatively similar between the two routes of administration. Quantitatively, however, the plasma concentrations of the metabolites were higher after the i.a. route. These results are in agreement with a previous study reported in rabbits, and suggest that deacetylation of DTZ and MA in the blood is extremely important in this species.