Magnesium sulfate is widely used as a food additive and as an orally administered medication. The aim ofthis study was to evaluate the possible cytotoxicity of magnesium sulfate on AGS human gastric adenocarcinomacells and gastric mucosa in mice. A trypan blue exclusion assay was used to determine the reduction in viabilityof AGS cells exposed to magnesium sulfate, and then effects on cell proliferation were quantified. The role ofmagnesium sulfate-mediated pro-inflammatory cytokine production in AGS cells was also investigated. mRNAexpression for IL-1β, IL-6, IL-8, and TNF-α was determined by RT-PCR, and secretion of these cytokines wasmeasured by ELISA. Immunohistochemical evaluation of IL-1β, IL-6, and TNF-α expression was conducted inmouse gastric mucosa. Addition of 3 to 50 mM magnesium sulfate to AGS cells inhibited both cell proliferationand cell viability in a dose-dependent manner. Magnesium sulfate had little effect on production of IL-1β or IL-6but significantly inhibited production of IL-8. The animal model demonstrated that magnesium sulfate inducedproduction of IL-1β, IL-6, and TNF-α. These preliminary data suggest that magnesium sulfate had a direct effecton the stomach and initiates cytotoxicity in moderate concentrations and time periods by inhibiting viabilitya nd proliferation of AGS cells and by regulating expression and/or release of pro-inflammatory cytokines.