Soluble microneedles (MNs) has recently become an efficient and minimally invasive tool in transdermal drug delivery because of their excellent biocompatibility and rapid dissolution. However, direct monitoring of the release of drug in vivo is a difficult task. The dissolution of MNs was monitored to estimate the delivery of drug by using optical coherence tomography (OCT); The performances of two soluble MN arrays made from polyvinyl alcohol (PVA) and polyvinyl alcohol/polyvinylpyrrolidone (PVA/PVP) were determined by calculating the crosssectional areas of the microchannels in mouse skin as a function of time. Results showed that the dissolution of these MNs could be observed in vivo via OCT in real time and could be quantitatively evaluated using OCT. The OCT images are useful in estimation and comparison of the performance of different MNs. Therefore, OCT is a potential tool in monitoring drug delivery by MNs in vivo.