Thermodynamic data of drug is important to industrial design and industrial application. In this paper, solubility data of tylosin in pure solvents and acetone +water mixture solvents were experimentally determined from 279.75 K to 323.15 K. The experiment results indicated that solubility of tylosin in pure solvents gradually decreased and followed this order: chloroform > butylacetate > acetonitrile > tetrahydrofuran > acetone > benzene > n-butanol > ethyl acetate > n-propanol > ethanol > methanol > water, and solubility gradually decreased with water increasing in water + acetone mixture solvents. Moreover, experimental solubility increased with temperature increasing except for water（xc ≥ 0.9281 + acetone mixture solvents. Thermodynamic models correlating solubility data showed that modiﬁed Apelblat model was litter better agreement than Van¢t Hoff model, Wilson model NRTL model in pure solvents and C/R-K model, Jouyban Acree model in acetone+water solvents by ARD,AMSD and R2. Furthermore, thermodynamic properties for dissolution process of tylosin were calculated and discussed by modiﬁed Apelblat model paramaters.