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An antiulcer drug, zinc l-carnosine (polaprezinc), provides gastric mucosal protection against various irritants. In this study, we evaluated the effects of zinc l-carnosine on expression of 72-kDa heat shock protein (HSP72, stress inducible HSP70), which is known as an endogenous cytoprotectant in a wide variety of cells, including rat gastric mucosa in vitro and in vivo. Expression of HSP72 after exposure to zinc l-carnosine, zinc sulfate, or l-carnosine (1–300 μM) in rat gastric mucosal cells (RGM1) and intragastric administration of zinc l-carnosine, zinc sulfate (30 or 100 mg/kg) and l-carnosine (76 mg/kg) was investigated by western blotting and densitometric analysis. Exposure to zinc l-carnosine and zinc sulfate increased the expression of HSP72 significantly in RGM1 cells. Intragastric administration of zinc l-carnosine and zinc sulfate showed significant increment in HSP72 in rat gastric mucosa also in vivo. The ability to induce HSP72 is significantly higher in zinc l-carnosine compared with zinc sulfate based on molecular concentration in vivo. However, l-carnosine did not increase the expression of HSP72 in vitro and in vivo. Zinc derivatives, especially zinc l-carnosine, could be a strong HSP72 (chaperon) inducer, which has been known to enhance mucosal protective ability.