In order to reveal the chemical substance basis of pharmacodynamic effects of Zuotai,energy dispersive spectrometry of X-ray (EDX),X-ray fluorescence spectroscopy (XRF),synchrotron radiation X-ray absorption fine structure (SR-XAFS),X-ray diffraction (XRD),scanning electron microscope (SEM) and atomic force microscope (AFM) were used to analyze the elements,the chemical valence and local structure of mercury,and the chemical phase composition and micro-morphology of Zuotai.EDX and XRF analysis shows that the main elements in Zuotai are Hg and S,with some other minor elements,such as O,Fe,Al,Cu,K,Ag,Ca,Mg etc.SR-XAFS analysis shows that:the oxidation state of mercury in Zuotai is divalence,its neighbor atoms are S,and its coordination number is four.XRD assay found that β-HgS (cubic,F-43m 216) and S8 (orthorhombic,Fddd 70) are the main phase compositions in Zuotai.Besides,it also has a small amount of C (hexagonal,P63/mmc 194),Fe1.05S0.95 (hexagonal,P63/mmc 194),Cu6S6 (hexagonal,P63/mmc 194),Cu1.8S (cubic,F-43m 216) and so on.And it was found that the crystallinity of Zuotai is about 59%,and the amorphous morphology substance in it is about 41%.SEM and AFM detection suggests that Zuotai is a kind of ancient micro-nano drug,and its particle size is mainly in the range of 100～600 nm,even less than 100 nm,which commonly further aggregate into several to 30 μm loose amorphous particles.In summary,the present study elucidated physicochemical characterization(elements composition,coordination information of mercury,phase composition and micro-morphology) of Zuotai,and it will play a positive role in promoting the interpretation of this mysterious drug.