Thermal and pH dual-sensitive hydrogel microspheres were fabricated using spray drying. During the spray drying, chemical crosslinks were formed in situ via the Diels-Alder reaction without the involvement of any catalysts or organic solvents. The structures and morphologies of the products were characterized by Fourier Transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), Raman spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). A general weighing method was applied to study the swelling behavior of the microspheres at different temperatures and pHs. Using urea as a model molecule, the ability of the microspheres to control the release of urea was explored by spectrophotometry and calculated from the calibration curve obtained from the reaction of urea and diaminobenzaldehyde. The as-prepared microspheres show a reversible and reproducible volume change with varying pH or temperature, and their swelling ratios increase with increasing temperature or pH. Furthermore, the urea release rates can be tuned by changing the pH or the temperature. Since spray drying can easily produce microspheres on a large scale, the strategy demonstrated here has the potential for applications in the green preparation of hydrogel microspheres. POLYM. ENG. SCI., 2019. (c) 2019 Society of Plastics Engineers