The solubility of azithromycin monohydrate in ethanol, propan-2-ol, butan-1-ol, ethyl ethanoate, and 2-propanone from 278.15 K to 323.15 K was measured by a synthetic method. The measured solubility data were correlated by van't Hoff equation, modified Apelblat equation, lambda h equation, Wilson, and NRTL models. It was found that the Wilson equations give the best correlation results. The mixing properties including the mixing free Gibbs energy, enthalpy, and entropy of azithromycin monohydrate were also calculated based on the Wilson model parameters. The results indicate that the dissolution process of azithromycin monohydrate in all tested solvents is spontaneous and endothermic.