The interaction between rofecoxib (ROF), an analgesic antiinflammatory drug, with β-cyclodextrin and HP-β-cyclodextrin was evaluated in aqueous environment and in solid state. The solubility of ROF with β-CyD and HP-β-CyD in aqueous solution was determined and the stability constants were calculated from the phase solubility studies at different temperatures. Binary systems of ROF with the investigated CyDs were prepared by co-grinding and solvent evaporation methods. The formation of inclusion complexes with β-CyD and HP-β-CyD in the solid state was investigated by differential scanning calorimetery, infrared spectroscopy and X-ray diffractometry. Dissolution rate of ROF binary systems was determined and compared with those of the physical mixture and the pure drug. It was found that the solubility of ROF increased as a function of both CyDs concentration and temperature showing an AL- type diagram indicating the formation of 1: 1 stoichiometric inclusion complexes. The apparent association constants were found to be 104.45 M-1 and 121.65 M-1 for β-CyD and HP-β-CyD; respectively. Co-grinding method led to enhancement of ROF dissolution rate in comparison to the other preparation methods. The in vitro dissolution rate of ROF at pH 7.4 could be ranked in the following order: ground mixture, coevaporate, physical mixture and pure drug. Ground mixture of ROF with HP- β-CyD and βCyD has a t50% = 7 min and 50 min, respectively.