Nowadays most of the CNS acting therapeutic molecules are failing in clinical trials due to efflux transporters at the blood brain barrier (BBB) which imparts resistance and poor ADMET properties of these molecules. CNS acting drug molecules interact with the BBB prior to their target site, so there is a need to develop predictive models for BBB permeability which can be used in the initial phases of drug discovery process. Most of the drug molecules are transported to the brain via passive diffusion which is explored extensively; on the other hand, the role of active efflux transporters in BBB permeability is unclear. Our aim is to develop predictive models for BBB permeability that include active efflux transporters. An in silico model has been developed to assess the role of BCRP on BBB permeation. Eight descriptors were selected, which also include BCRP substrate probabilities used for model development and show a relationship between BCRP and logBB. From our analysis, it was found that 11 molecules satisfied all criteria required for BBB permeation but have low logBB values. These 11 molecules are predicted as BCRP substrates from the model developed, suggesting that the molecules are effluxed by the BCRP transporter. This predictive ability was further validated by docking of these 11 molecules into BCRP protein. This study provides a new mechanistic insight into correlation of low logBB values and efflux mechanism of BCRP in BBB.