A high-performance liquid chromatography method with solid-phase extraction is introduced for the determination of geniposide in rat urine after oral administration of yin-zhi-ku decoction. Geniposide and an internal standard (paeoniflorin) are extracted from urine using Strata cartridges. Analysis of the extract is then performed on a reversed-phase C18 column using acetonitrile-water (14:86, v/v) as eluting solvent system. UV detection is set at 238 nm. The calibration curve for geniposide is linear (r = 0.9996) in the concentration range of 2.0-240 microg/mL. Both intra- and interday precision of the geniposide are determined, and their relative standard deviation does not exceed 10%. The validated method is successfully applied to determine geniposide from rat urine after oral administration of yin-zhi-ku decoction.