Abstract: The present study aimed to improve the solubility and ultimate bioavailability of poorly soluble Mefloquinehydrochloride, an antimalarial drug by encapsulating it in α-cyclodextrin and Hydroxy propyl α- cyclodextrin. Effect of these complexes was studied by UV-VIS spectroscopy, Fluorescence spectroscopy, Phase solubility study, SEM-EDS and FTIR spectroscopy. The association constant of the inclusion complexes were determined by the Benesi- hilde – brand relation and the inclusion ratio was found to be 1:1. The water solubility of Mefloquinehydrochloride was increased by inclusion with α-CD and HP-α-CD according to the phase solubility diagram.The results obtained from SEM-EDS and FTIR spectroscopy confirmed the inclusion of Mefloquinehydrochloride into cyclodextrins cavity.