Abstract: AimTo study the relationship between resonance Rayleigh scattering(RRS) and the formation of association nanoparticle, and to develop a new and sensitive RRS method for the determination of trace berberine(BB). MethodsThe association nanoparticle between BB and tetraphenylboron(TPB) was investigated by means of RRS, absorption spectral method and transmission electron microscope (TEM). ResultsIn pH 5.0 NaAc-HAc buffer solution, BB and TPB combine to BB-TPB association complex. The association complexes aggregate to (BB-TPB)_nassociation nanoparticles, due to the strong hydrophobic force and Van der Waals force. It exhibits a resonance Rayleigh scattering peak at 470 nm, a maximum absorption peak at 368 nm. A new RRS method was proposed for the determination of 0.06 to 5.28 mg·L^-1 BB in real samples with satisfactory results. The detection limit is 26 μg·L^-1. ConclusionThe TEM of (BB_jAg_p-TPBj+p)h composite association nanoparticles was observed by means of composite association nanoreaction both TPB^-and BB⁺ or Ag⁺. The results indicated that the formation of (BB-TPB)_nassociation nanoparticles and interface of solid-liquid results in the enhanced resonance light-scattering. This new RRS method showed high sensitivity, and had been successfully applied to the determination of BB in real samples.