An ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method coupled with molecularly imprinted solid phase extraction (MISPE) for rapid determination of 15 β 2-agonists residues in swine urine has been established. In order to obtain the optimized purification conditions, different pH values of loading, washing and elution solvents for the MISPE procedure were optimized. Finally, the swine urine samples (pH 7.0) were performed directly by MISPE column, then the column was washed with water, acetonitrile and 0.5%(v/v) acetic acid in acetonitrile, and eluted with 10%(v/v) acetic acid in methanol. Meanwhile, the parameters of UPLC-MS/MS have been optimized.The UPLC separation was performed on a BEH C18 column, and eluted with the mobile phase consisting of 0.1%(v/v) formic acid aqueous solution and acetonitrile with linear gradient program. The analysis was in ESI positive ion scan mode and multiple reaction monitoring (MRM) mode. Under the optimum conditions, the blank swine urine was spiked with different concentrations analytes and taken for analysis to evaluate the established method. To highlight the advantage of MISPE, specificity adsorption for the 15 β 2-agonists in swine urine was investigate. The linear ranges were 0.1-20 μ g/L for the 15 β 2-agonists ( r 2≥0.992). The limits of detection (LODs) and the limits of quantification (LOQs) were 0.03 and 0.1 μ g/L, respectively. At the spiked levels of 0.1, 0.5 and 2.5 μ g/L in blank samples, the mean recoveries were 65.6%-115.0% with the relative standard deviations (RSDs, n=6) of 0.57%-16.1%. Overall, the proposed method is simple, quick, reliable,sensitive, and can be applied in large scale supervision of illegal usage of the 15 β 2-agonists.