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To study the effects of different chemical factors in the gastrointestinal tract, I.e. pH, proteins, amino acids,ionic strength and Na2S, on the dissolution of cinnabar. The content of the total mercury in various dissolutions of cinnabar was analyzed by UV/VIS Spectrophotometer. Laser Particle Size Analyzer measured the particle distributionsin the dissolution of cinnabar. The chemical species of dis-solved substance of cinnabar in the presence of Na2S were determined using ESI-MS. The results indicate that the solu-bility of cinnabar could be increased significantly in the pres-ence ofNa2S/S0, and strong acidic pH, respectively. While theinfluence of thiol amino acid on promoting dissolutionremains relatively low. Cinnabar did not dissolve in the form of nanoparticle. It is postulated that cinnabar could be dissolved in the gastrointestinal tract in various forms of sulfur-containing mercury complexes.