Background: The blood brain barrier (BBB) is acknowledged to inhibit the distribution of drugs into the brain.  To overcome this issue, a number of brain-targeting ligands such as glucose, insulin and transferrin have been used widely.  However, the brain targeting ability of these ligands is insufficient.  Objective: In the present study, we serendipitously revealed the potentials of lactose as a ligand for brain.  Therefore, to develop a novel drug carrier for brain, we newly fabricated lactose-appended 2-hydroxypropyl-b-cyclodextrin (Lac-HP-b-CyD), and evaluated its in vitro permeability against BBB and accumulation in the brain in vivo.  Materials and Methods: First, to establish an in vitro BBB model, hCMEC/D3 cells, a human brain endothelial cell line, and SH-SY5Y cells, a human neuroblastoma cell line, were cultured in the upper and lower compartment of Transwell^®, respectively.  Then, the  permeability of Lac-HP-b-CyD against the in vitro BBB model was evaluated.  Cellular uptake of Lac-HP-b-CyD in SH-SY5Y cells was assayed with a confocal laser scanning microscopy and flow cytometer.  In addition, BALB/c mice were intravenously injected with Lac-HP-b-CyD and its accumulation in the brain was observed by an in vivo imaging system (IVIS). Results: Permeability of Lac-HP-b-CyD against the in vitro BBB model was drastically increased, compared to that of HP-b-CyD.　In addition, Lac-HP-b-CyD showed high cellular uptake in SH-SY5Y cells after the penetration of monolayer of hCMEC/D3 cells, compared to HP-b-CyD.  Moreover, Lac-HP-b-CyD significantly accumulated in the brain after intravenous administration to BALB/c mice, compared to HP-b-CyD. Conclusion: These findings suggest that Lac-HP-b-CyD has a potential as a novel drug carrier for brain.