Our previous studies show that Helicobacter pylori (H. pylori) induces oxidative stress and the expression of proinflammatory cytokines in gastric epithelial cells. H. pylori induces the expression of molecular chaperones and proteins involved in protein-folding machinery as a defense mechanism against cellular stress. The suppressors of cytokine signaling (SOCS) are known as negative regulators of major immune signal pathways. The purpose of this article is to determine whether H. pylori in a Korean isolate (HP99) induces the expression of SOCS in rat gastric mucosal RGM-1 cells as a defense mechanism. As a result, HP99 induced SOCS-3 expression time-dependently in RGM-1 cells. SOCS-1 was not expressed while SOCS-2 expression was not changed by HP99 infection in RGM-1 cells. SOCS-3 might have a defensive role in H. pylori-infected gastric mucosal cells. Further study by manipulating SOCS-3 gene should be performed to investigate the physiological meaning of SOCS-3 induced by H. pylori in gastric mucosal cells.