We investigated the delivery of rhodamine B and Oregon Green^®-labeled paclitaxel (OGLP) in ex vivo porcine carotid artery wall (CAW) samples after heating the reagents to 50–70℃ for 15 s. When the isolated CAW samples were placed in the heated fluorophore solutions, the penetration depth of the hydrophobic rhodamine B increased significantly compared with reference solution at 37℃. The penetration depth of OGLP also tended to increase upon heating to 70℃ for 15 s. We also studied the mechanism of this agent delivery enhancement by observing the inner surface structure and hydrophobicity of the CAW samples after heating. An expanded mesh structure at the inner surface of the heated CAW samples was observed upon heating above 70℃, and the mean hydrophobicity of the media layer also increased significantly. We hypothesize that heating at 60–70℃ for 15 s enhances the delivery of fluorophores to CAW samples as a result of an expanded mesh structure at the inner surface of the CAW, along with a simultaneous increase in hydrophobicity.