Abstract: Novel analyte-responsive inverse-opal hydrogels (IOHs) based on molecular imprinting technology were fabricated to generate a highly selective and sensitive device for the colorimetric detection of tetracycline (TC). The TC-responsive IOHs were constructed by packing periodic silica-air arrays and then photo-polymerizing TC-containing hydrogels between the closely packed silica microspheres. Next, the original silica microspheres were etched, and the TC template molecules were eluted with the remaining hydrogel-air arrays. The abundant imprinted sites in the thin hydrogel walls specifically rebound TC via hydrogen bonds, leading to a periodic spacing change and a Bragg diffraction peak shift that converted the rebinding events into readable optical signals. The TC-responsive IOHs offered favorable linearity over four orders of magnitude (10-10 - 10-6 mol/L) with Bragg diffraction peak blue shift of approximately 43 nm. Excellent recognition selectivity for TC over its analogue was also attained. Furthermore, the TC-responsive IOHs were successfully applied to detect TC in food samples of milk and meat, with high recoveries of 88.9-112.0% and 87.0-108.7%, respectively. Using TC as a model, the imprinted analyte-responsive IOHs show great potentials as a rapid and cost-effective method for direct, label-free and sensitive colorimetric measurements of trace pollutants in complicated samples