We demonstrate a facile method for fabricating novel 3D microfluidic channels by using two-photon-activated chemistry to locally switch the interior surface of a porous host from a hydrophobic state to a hydrophilic state. The 3D structures can be infilled selectively with water and/or hydrophobic oil with a minimum feature size of only a few micrometers. We envision that this approach may enable the fabrication of complex microftuidic structures that cannot be easily formed via current technologies.