Abstract: With Glew-Hildebrand saturation technique,aqueous solubilities of Ofloxacin.Nor floxacin and Pipemidic acid are measured at different temperatures by HPLC and artificial neural network technique,respectively.Given to the solubilities of quinolone medicines,a solubility model is proposed by using chemical engineering thermodynamic theory.This model is veritied by experimental and reference data.A new molecular topological index is proposed with extensive distance atrix,which can describe the molecular structures of hetero-atom,multi-bonds and comp1ex-cycle compounds.Finally,the a mode1 relating solubility to molecular structure is ob tained by using the experimental solubility data of these three kinds of uinolones.Based on this model,the solubilities of nine quinolones,such as Fleroxacin,at 25℃ and 37℃ are predicted and the results are in good agreement with experimental data．