This report intended to study the potential of liposome EKC (LEKC) as a convenient and high-throughput screening tool to assess drug penetration across the blood-brain barrier (BBB). The retention factors (k) of 24 structurally diverse compounds were determined with LEKC and vesicle EKC (VEKC), respectively. Principal component analysis of the steadystate concentrations ratio of compounds in the brain and in the blood expressed as log BB, log k(LEKC), log k(VEKC), and other lipophilic descriptors including octanol/water partition coefficient (Clog P), octanol/water distribution coefficients (log D-7.4), and polar surface area. (PSA), showed the maximum similarity of partitioning processes in LEKC to drug penetration across the BBB. Furthermore, the log BB were correlated with the above five lipophilic descriptors, and the results showed that log kLEKC gave the better correlation coefficient (r(2)=0.811, p<0.0001) than those of log D-7.4, Clog P, PSA, and log k(VEKC) (r(2)=0.730, 0.672, 0.627, and 0.620, p<0.0001). This is the first report of the use of LEKC as a promising rapid tool to profile drug penetration across the BBB.