This report describes, for the first time, cucurbit[7]uril-assisted quantitative in vitro and in vivo uptake of a hydrophobic model drug, coumarin-6, by both an epithelial cell model and a zebrafish model. The transcellular delivery pathway study suggested multiple mechanisms involved, including macropinocytosis, clathrin and lipid raft-mediated endocytosis/exocytosis.