In the current study, the solubility of mesalazine in the binary mixtures of propylene glycol (PG) + 2-propanol was determined using a shake flask method followed by UV-Vis spectroscopy method. The results showed that the maximum solubility was obtained in neat PG (xm= 4.57 × 10− 4) at 313.2 K and the minimum solubility in the neat 2-propanol (xm= 6.32 × 10− 5) at 293.2 K. In the next step, all data were fitted/back-calculated to several mathematical cosolvency models. Deviations of back-calculated data from experimental values (< 4.0%) show the applicability of the models for the prediction of solubility of meselazine in binary mixtures selected. For saturated systems, density data were also determined and fitted to the adopted form of the Jouyban-Acree model (back-calculated MRD% values were within 0.2%). Furthermore, the thermodynamic behavior of mesalazine in the PG + 2-propanol mixtures was investigated using the Gibbs energy, enthalpy, and entropy calculations at Thm.