A rapid and simple method of highperformance liquid chromatography with UV detector for the quantifi-cation of glycyrrhetinic acid (GA) in mice plasma and tissues has been developed and validated. With theestablished assay method, the pharmacokinetic profiles and tissue distribution of GA in different formu-lations are compared in mice after intravenous administration of the drug (25mg/kg). The results showedthat mPEG-PLA modified (mPEGylated) GA liposome (PL-GA) significantly prolonged the mean residencetime (MRT) of GA in mice plasma and liver (MRT: 0.43±0.13 and 1.72±0.11h, respectively) than the nor-malGAliposome(L-GA (MRT:0.23±0.01and1.07±0.31h,respectively)andGAsodiuminjection(S-GA)(MRT: 0.13±0.01 and 0.95±0.08h, respectively). Moreover, PL-GA specifically increased GA uptake inliver (AUC0–∞,livervalue of 1.6-fold and 1.3-fold higher than that for S-GA and L-GA, respectively) andreduced its distribution into other tissues after dosing. Due to these pharmacokinetic properties, it maybe promising to develop PL-GA further as a new pharmaceutical preparation for GA on the treatment ofvarious chronic hepatic diseases.