By preparing an inclusion complex of paeonol (PAE) with β-cyclodextrin (β-CD), this study investigated its release behavior from thermo-sensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels. The PAE-β-CD complex was prepared via coprecipitation. According to differential scanning calorimeter (DSC) and X-ray diffraction (XRD) results, the solid PAE-β-CD complex was found in the amorphous state, indicating that each PAE molecule was encapsulated by a β-CD molecule. The change of chemical shifts of H3 and H5 in proton nuclear magnetic resonance (H NMR) spectra indicated that PAE was inside the CD cavity. PNIPAAm hydrogels containing different cross-linker contents were then synthesized and had a similar lowest critical solution temperature (LCST) of around 33°C. Experimental results of swelling and deswelling indicated that increasing the cross-linker content of the hydrogel decreased the swelling ratio and increased the water retention. According to experimental results of PAE-β-CD complex release, the release rate at 45°C (>LCST) was higher than at 25°C (<LCST). Moreover a lower cross-linker content the hydrogel contained implies a higher rate of PAE-β-CD complex release. Above results suggest that the release of PAE-β-CD complex is related to the volume contraction of the hydrogel, which is affected by hydrogel compositions and release temperatures.