The solubility of imatinib mesylate in nine monosolvents and two binary solvents was determined by the shaken flask method followed by UV composition analysis from 278.15 to 318.15 K at atmospheric pressure. The solubility increases with the increasing of temperature in all solvents we chose. Meanwhile, the dissolving capacity of imatinib mesylate ranks as methyl acetate < 2-propanol < acetonitrile < isobutanol < 1-butanol < tetrahydrofuran < 1-propanol < ethanol < methanol. The Apelblat model, lambda h equation, and nonrandom two-liquid (NRTL) model described the solubility data of imatinib mesylate in monosolvents; simultaneously, the Apelblat model, combined nearly ideal binary solvent/Redlich-Kister model, and NRTL model were employed in binary solvents. The results show a satisfactory correlation with the experimental data. Additionally, mixing thermodynamic properties of imatinib mesylate were calculated based on the NRTL model, which reveals the mixing process is spontaneous and exothermic.