2,4,6-trihydroxy-3-geranylacetophenone (tHGA) is a bioactive compound that shows excellent anti-inflammatory properties . However, its pharmacokinetics and metabolism have yet to be evaluated . In this study, a sensitive LC-HRMS method was developed and validated to quantify tHGA in rat plasma . The method showed good linearity (0.5-80 ng/mL). The accuracy and precision were within 10% . Pharmacokinetic investigations were performed on three groups of six rats . The first two groups were given oral administrations of unformulated and liposome-encapsulated tHGA, respectively, while the third group received intraperitoneal administration of liposome-encapsulated tHGA . The maximum concentration (C), the time required to reach C (t), elimination half-life (t) and area under curve (AUC) values for intraperitoneal administration were 54.6 ng/mL , 1.5 h , 6.7 h, and 193.9 ng/mL·h, respectively . For the oral administration of unformulated and formulated tHGA, C values were 5.4 and 14.5 ng/mL, t values were 0.25 h for both, t values were 6.9 and 6.6 h, and AUC values were 17.6 and 40.7 ng/mL·h, respectively . The liposomal formulation improved the relative oral bioavailability of tHGA from 9.1% to 21.0% which was a 2.3-fold increment . Further, a total of 12 metabolites were detected and structurally characterized . The metabolites were mainly products of oxidation and glucuronide conjugation.