In this work, two new polymorphs of dirithromycin were discovered and successfully prepared. Both polymorphs were characterized and identified by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) techniques. The solubility of these two polymorphs in four pure solvents and a binary solvents mixture was measured by using a static gravimetric method over the temperature range from 273.15 K to 313.15 K. The experimental solubility data in pure solvents were correlated with modified Apelbat equation, the lambda h equation and the NRTL model. CNIBS/R-K model and the Jouybane-Acree model were employed to correlate the solubility data in mixed solvent systems. All the fitting processes could obtain satisfactory correlation results. Finally, the thermodynamic properties of these two forms of dirithromycin in all the solvents above were investigated and discussed based on the solubility data and the NRTL model. The results indicated that the mixing process was endothermic, spontaneous and entropy favorable in all the investigated solvents. (C) 2018 Elsevier Ltd.