The pharmacokinetics of senkyunolide A, one of the major bioactive ingredients in the traditional Chinese medicinal herb Rhizoma Chuanxiong, which is commonly used for the treatment of cardiovascular diseases, was studied in rats. After intravenous (IV) administration, senkyunolide A was extensively distributed (Vd/F: 6.74 ± 0.73 L/kg) and rapidly eliminated from the plasma (CL/F: 7.20 ± 0.48 L/h per kilogram and t1/2: 0.65 ± 0.06 hr). Hepatic metabolism was suggested as the major route of senkyunolide A elimination as indicated by the results of in vitro S9 fraction study. After intraperitoneal (IP) administration, senkyunolide A exhibited dose-independent pharmacokinetics. The absorption after IP administration was rapid (Tmax: 0.04 ± 0.01 hours), and the bioavailability was 75%. After oral administration, senkyunolide A was also absorbed rapidly (Tmax: 0.21 ± 0.08 hours); however, its oral bioavailability was low (∼8%). The contributing factors were determined to be instability in the gastrointestinal tract (accounting for 67% of the loss) and hepatic first-pass metabolism (accounting for another 25%). Pharmacokinetics of senkyunolide A were unaltered when Chuanxiong extract was administered, which suggests that components in the extract have insignificant effects on senkyunolide A pharmacokinetics.