Abstract: OBJECTIVE To establish a high-performance liquid chromatography method for determination of sorafenib, explore a method of measuring the sorafenib concentration in rat blood plasma. METHODS Agilent Eclipse XDB-C₁₈ column (150 mm×4.6 mm, 5 μm) was used. The mobile phase was 35%(0.05% formic acid and 0.05% triethylamine) in aqueous solution and 65% acetonitrile while the flow rate was 1.0 mL·min^-1. The column temperature was 30 ℃. The detection wavelength was 265 nm. RESULTS The standard curve of sorafenib concentration was linear in the range of 0.4-12 μg·mL^-1(r=0.999 9). The average recovery rate of the method was 100.8%, RSD was 1.470%. The rat was treated by gavage with sorafenib at the dosage of 65 mg·kg^-1. The sorafenib concentration in rat blood plasm was 2.830 μg·mL^-1. CONCLUSION The method is suitable for the determination of sorafenib. It is practicable, simple, sensitive, and can be used to measure the sorafenib concentration in rat blood plasma.