OBJECTIVE To determine the concentration of matrine in rats plasma and tissue and study the pharmacokinetics and tissues distribution of matrine solution (MS), regular matrine liposome (ML) and stealth matrine liposome (LML) after the intravenous administration at a single dose of 15 mg x kg(-1) to rats. METHODS Reversed-phase HPLC was used to determine matrine concentration in rats plasma and tissues. RESULTS The concentration-time curves of MS, ML and LML were fitted to a two-compartment model. The terminal half-life of LML was 2.7-fold higher than MS and 2-fold higher than ML. The area under the plasma concentration curve (AUC) of LML was 63-fold higher than MS and 2.3-fold higher than ML. Tissues distribution results proved that the area under the plasma concentration curve of LML was significantly different from ML and MS (P<0.05). The area under the liver and spleen curve of LML was significantly different from ML (P<0.05). The ratio between the area under the curve of plasma and the area under the curve of reticulo-endothelial system (Blood/RES) of LML was 5.4-fold higher than ML. CONCLUSIONS Our present studies demonstrate that, compared to MS and ML, LML significantly alters its pharmacokinetics in plasma and tissues targeting.