Abstract: OBJECTIVE To establish a new high sensitivity resonance Rayleigh scattering(RRS) method for the rapid and accurate determination of mesna in drugs. METHODS In the weakly basic solution of BR, bright green was combined with mesna by electrostatic interaction to form ionic association complex, which led to a significantly enhanced of the RRS signal. The RRS intensity had a good linear relationship with mesna concentration at the peak of the maximum RRS. The detection wavelength was 344 nm. RESULTS In a BR buffer solution of pH 7.75, bright green combined with mesna to form a green binary ionic association. New RRS spectra with characteristic peaks at 294, 344, 468 nm was produced. The maximum RRS peak was located at 344 nm, linear range was 0.006-0.41 mg·L^-1, the detection limit was 0.005 2 mg·L^-1. This method had been applied to determine the content of mesna in commercially available mesna drugs, with the spiked recoveries and relative standard deviations(RSD, n=6) were 98.3% to 103% and 1.6% to 2.3%, respectively. CONCLUSION The method is simple, rapid. It has high sensitivity and selectivity, and it is suggested to be applied to the determination of mesna in the actual drug.