Determination of passive permeability is not only important for predicting oral absorption and brain penetration, but also for accurately predicting hepatic clearance. High throughput (HT) measurement of passive permeability across hepatocyte cell membrane is technically more challenging than using monolayer cell-based permeability assays. In this study, we evaluated if the HT Madin-Darby canine kidney II-low efflux (MDCKII-LE) cell monolayer permeability assay can be used as a surrogate to predict the passive permeability of hepatocytes. Apparent passive permeability of MDCKII-LE is well correlated to passive diffusion clearance of human and rat hepatocytes, suggesting that the HT MDCKII-LE assay can be used as a surrogate to estimate the passive permeability of hepatocytes. In addition, lipophilicity (Log D determined at pH 7.4) was also found to be well correlated with both MDCKII-LE and hepatocyte permeability for most compounds, hence it may serve as another permeability surrogate.