Abstract: Na-modified Ca-montmorillonite (Ca-MMT ) was successfully prepared by a microwave-mechanochemistry technique. A new composite based on drug cetirizine hydrochloride (CTH) and Na-montmorillonite (Na-MMT) was prepared by the ion-exchange method, and the adsorption characteristics of CTH onto Na-MMT were evaluated. Through Fourier transformed infrared (FTIR) and X-ray diff raction (XRD) analyses, the st ructure of the resulted CTH/MMT composite was confirmed. The in vitro drug release research of the CTH/MMT composite in both artificial simulated gastric juice (ASGJ) and artificial simulated intestinal juice (ASIJ ) was used to study the efficiency, mechanism and kinetics of the drug release process. The results show that CTH intercalates in Na-MMT, and the interlayer spacing increases from 1. 25 nm to 2. 13 nm. The adsorption kinetics is found to follow the pseudo-second-order kinetic model. The adsorption equilibrium data corresponds to Freundlich model. In vitro experiment s show that CTH/MMT has a good sustained-release effect, and MMT can be used as a controlled-release carrier for CTH.