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A sensitive liquid chromatography-mass spectrometric (LC/MS) method for the quantification of ginsenoside Rg2 (Rg2) in rat plasma was developed after solid-phase extraction (SPE). Chromatographic separation was achieved on a reversed-phase Kromasil C 18 column with the mobile phase of acetonitrile-ammonium chloride (500 µM/L) and step gradient elution resulted in a total run time of about 9 min. The analytes were detected using electrospray negative ionization mass spectrometry in the selected ion monitoring (SIM) mode. A good linear relationship was obtained in the concentration range (5–2500 ng/mL) (r=0.9999). Limit of quantification (LOQ) was 5 ng/mL and the limit of detection (LOD) was 2 ng/mL using 100 µL plasma sample. Average recoveries ranged from 72.43–84.73% in plasma at the concentrations of 20, 200, and 2000 ng/mL. Intra- and interday coefficients of variation for the assay were 4.93–10.87% and 4.06–7.84%, respectively. The method was successfully applied to the analysis of ginsenoside Rg2 in rat plasma. The applicability of this assay was examined in a preliminary pharmacokinetic study of ginsenoside Rg2 in rats. [ABSTRACT FROM AUTHOR]