In pH 4.5 Britton-Robinson(BR)buffer solution,erythrosin(ET)can react with diphenhydramine(DP)to form a 1:1 ion-association complex,which not only results in the change of the absorption spectra,but also results in the great enhancement of resonance Rayleigh scattering(RRS)and the quenching of fluorescence.Furthermore,a new RRS spectrum will appear,and the maximum RRS wavelength was located at about 580 nm.In this work,the spectral characteristics of the absorption,fluorescence and RRS,the optimum conditions of the reaction and the properties of an analytical chemistry were inves- tigated.A sensitive,simple and new method for the determination of DP by using erythrosin as a probe has been developed.The detection limits for DP were 0.0020μg/mL for RRS method,0.088μg/mL for absorption method and 0.094μg/mL for fluorophotometry.There was a linear relationship between the absorbance,RRS and fluorescence intensities and the drug concentration in the range of 0.0067-2.0, 0.29-6.4 and 0.31-3.2μg/mL,respectively.The effects of the interaction of diphenhydramine and erythrosin on the absorption,fluorescence and resonance Rayleigh scattering spectra were discussed. In light polarization experiment,the polarization of RRS at maximum wavelength was measured to be P =0.9779,and it revealed that the RRS spectrum of DP-ET complex consists mostly of resonance scat- tering and few resonance fluorescence.In this study,enthalpy of formation and mean polarizability were calculated by AM1 quantum chemistry method.In addition,the reaction mechanism and the rea- sons for the enhancement of scattering spectra and the energy transfer between absorption,fluores- cence and RRS were discussed. In pH 4.5 Britton-Robinson (BR) buffer solution, erythrosin (ET) can react with diphenhydramine (DP) to form a 1: 1 ion-association complex, which not only results in the change of the absorption spectra, but also results in the great enhancement of resonance Rayleigh scattering (RRS) and the quenching of fluorescence. Future, a new RRS spectrum will appear, and the maximum RRS wavelength was located at about 580 nm. this work, the spectral characteristics of the absorption, fluorescence and RRS, the optimum conditions of the reaction and the properties of an analytical chemistry were in tigated. A sensitive, simple and new method for the determination of DP by using erythrosin as a probe has been developed. The detection limits for DP were 0.0020 μg / mL for RRS method, 0.088 μg / mL for absorption method and 0.094 μg / mL for fluorophotometry. There was a linear relationship between the absorbance, RRS and fluorescence intensities and the drug concentration in the range of 0.0067-2.0, 0.29-6.4 and 0.31 -3.2 μg / mL, respectively. These effects of the interaction of diphenhydramine and erythrosin on the absorption, fluorescence and resonance Rayleigh scattering spectra were discussed. In light polarization experiment, the polarization of RRS at maximum wavelength was measured to be P = 0.9779, and it revealed that the RRS spectrum of DP-ET complex consists mostly of resonance scatter and few resonance fluorescence. In this study, enthalpy of formation and mean polarizability were calculated by AM1 quantum chemistry method. addition, the reaction mechanism and the rea- sons for the enhancement of scattering spectra and the energy transfer between absorption, fluorescene and RRS were discussed.