The solubility of enrofloxacin in ethanol, water, 2-propanol, acetonitrile, and acetic ether was measured by a static analytical method from (303.15 to 321.05) K. The concentrations of enrofloxacin in saturated solvent were analyzed by UV spectrometry. The experimental solubility data for pure solvents decreases in the order acetonitrile > acetic ether >2-propanol > ethanol > water. The experimental solubility data was correlated by the modified Apelblat equation, the ideal solution equation, and the Clarke-Glew equation. The results show that the mole fraction solubility of enrofloxacin in pure solvents increased with increasing temperature; the Clarke-Glew two parameters equation (Clarke-Glew 2 equation) can provide a more accurate mathematical model than the modified Apelblat equation, the ideal solution equation, and the Clarke-Glew three parameters equation (Clarke-Glew 3 equation). In addition, the discussion of Gibbs energy, enthalpy, and entropy for enrofloxacin in different solvents indicated that the dissolution process of enrofloxacin was endothermic and entropy-driven.