This study was designed to elucidate the pharmacokinetics, absorption, tissue distribution and plasma protein binding properties of tanshinone IIA, a highly lipophilic compound isolated from Salvia miltiorrhiza. Tanshinone IIA was isolated using a previously well developed LC-MS/MS method. Its pharmacokinetic characteristics, absolute bioavailability, tissue distribution and plasma protein binding properties were determined. The membrane permeability was evaluated using Caco-2 cells in monolayer. The pharmacokinetic plasma profile of tanshinone IIA after a single intravenous dosing exhibited a triexponential pattern consisting of rapid distribution (t1/2 alpha, 0.024 h), slow redistribution (t1/2 beta, 0.34 h) and terminal elimination phase (t1/2 gamma, 7.5 h). Tanshinone IIA preferentially distributed into the reticuloendothelial system, especially into liver and lung, after either intravenous or oral doses. Tanshinone IIA (99.2 %) bound highly to plasma proteins, among which lipoprotein played an important role (77.5 %). Tanshinone IIA absorption was extremely poor with an absolute bioavailability below 3.5 %. Absorptive saturation was deduced from the fact that the AUC and Cmax increased less proportionally to dose and Tmax was significantly prolonged. The poor absorption of tanshinone IIA may be caused by its low aqueous solubility and limited membrane permeability. There were no significant differences of the apparent permeability coefficient for all tested concentrations and for the apical to basolateral and reverse direction transport, suggesting a passive transport mode and no involvement of an efflux protein. In conclusion, tanshinone IIA has a suitable pharmacokinetic behavior except for its poor absorption. A pharmaceutical strategy for promoting its absorption should be designed to develop tanshinone IIA as a new drug candidate.