In this paper, a three-dimensional (3D) poly(lactic-co-glycolic acid) (PLGA)/silica colloidal crystal drug delivery system with sustained drug release and visualized release monitoring was developed. This system had employed silica colloidal crystal microparticles as template skeleton, PLGA as drug carrier and dexamethasone (DEX) as therapeutic agent. The fabrication of the microparticle-based system included droplet formation based-on microfluidics, silica nanoparticle self-assembly and layer-by-layer deposition of PLGA containing DEX. In 370 mu m droplets, the silica colloidal nanoparticles could self-assemble orderly into microparticles with a diameter of 187 mu m, featuring red structure color. During the deposition of PLGA with the drug into the voids of the template microparticles, the reflection peak red-shifted and weakened until the voids were completely filled. Owing to the gradual degradation of PLGA, the release of DEX was triggered and sustained for 4 weeks with a cumulative release of 94.9%, while the structure color of the microparticles recovered during the release process. The color change could be recognized by the naked eyes, which would benefit the non-invasive monitoring of the drug release. The in vitro cytotoxicity and long-term inhibiting proliferation were investigated on retinal pigment epithelial cells. The inhibition effect of DEX released from the microparticles showed concentration-dependence from 40 to 200 mu g mL(-1) and time-dependence within 7 days. As a sustained drug delivery system with self-reporting drug release, the particles have potential applications in treatment of intraocular diseases. (C) 2018 Published by Elsevier Inc.