A method based on liquid chromatography-tandem mass spectrometry(LC-MS/MS) with solid supported liquid-liquid extraction was developed for the determination of cyclosporin A in human whole blood.The whole blood sample was loaded on the solid supported liquid-liquid extraction column after protein precipitation,and then eluted with methyl tert butyl ether.The extract was injected into a Shim pack XR-ODS(75 mm×3.0 mm i.d.,2.2 μm) column for separation,followed by detection of mass spectrometry in multiple reaction monitoring mode via an electrospray ionization interface.The quantitation was achieved using cyclosporin D as the internal standard.There was a good linearity for the method toward cyclosporin A in the range of 1.5-500 μg/L with a correlation coefficient(r) of 0.998.The limits of detection and quantitation were down to 0.5 μg/L and 1.5 μg/L,respectively.The average recoveries for the analyte at three spiked levels ranged from 78.6% to 83.5% with the intra day and inter day relative standard deviations of 3.1%-5.6% and 4.5%-8.3%,respectively.This method is suitable for the determination of cyclosporin A in whole blood sample due to its advantages of simplicity,rapidness,accuracy and reliability.