<p>In the current work, the solubility studies of mesalazine were performed in 1,4-dioxane + water mixtures at five different temperatures (293.2–313.2K). The experimental solubility data were correlated with some linear and non-linear cosolvency models (<i>i.e.</i>, the van’t Hoff, the Jouyban-Acree, and modified Wilson). The maximum solubility of mesalazine in mole fraction unit was 2.75 × 10^–4 in neat 1,4-dioxane at 313.2K and the minimum solubility was 1.20 × 10^–4 in water at 293.2K. The accuracy of the cosolvency models was investigated with the mean relative deviations for solubility prediction of the back-calculated solubility data against experimental values, and results showed high accuracy with <i>MRD</i>s% (&lt; 9.0%). The Gibbs energy, enthalpy, and entropy were calculated utilizing the van’t Hoff and Gibbs equations. Moreover, the density values for saturated mixtures were measured and represented by the Jouyban-Acree model. This study provides, for the first time, the determination of experimental solubility data of mesalazine in 1,4-dioxane + water mixtures.</p>