Abstract: In this study, we developed a sensitive and rapid HPLC-MS/MS method for the determination of trans-ferulic acid (trans-FA) in plasma samples, and investigated the pharmacokinetics characteristics in healthy volunteers. The plasma samples were extracted with acetic ether, and then separated on a Hedera ODS-2 column with a mobile phase of methanol and 5 mmol·L^-1 ammonium acetate buffer solution containing 0.05% acetic acid (34:66) at a flow rate of 0.4 mL·min^-1. Electrospray ionization source was applied and operated in the positive ion mode using MRM. The method exhibited a good linearity over the concentration range of 0.1-5 ng·mL^-1 (r ≥ 0.9992). The values on both the occasions (intra-and inter-day) were all within 9.2%, and the accuracy was 95.4%-111.4%. No matrix effect and carry-over effect were observed. Trans-FA was stable in human plasma under different storage conditions. The developed HPLC-MS/MS method is rapid, sensitive, accurate, and reproducible, and suitable for the pharmacokinetic study of trans-FA in healthy Chinese volunteers.