Background: Epigallocatechin-3-gallate (EGCG) is a major catechin of green tea; it has protective effects against injury and exhibits anti-inflammatory activity. Helicobacter pylori (H. pylori) eradication rates with clarithromycin-based triple therapy are declining, and an alternative strategy is urgently needed. The activity of EGCG against H. pylori-infected gastritis was investigated in an in vivo Mongolian gerbil model. Methods: Mongolian gerbils were randomly divided into H. pylori-infected, H. pylori-infected + drinking water containing 0.05% EGCG, triple treatment (amoxicillin, clarithromycin and esomeprazole), and control groups. After 12 weeks, gastric pH tests and histopathological evaluations were performed, and mucosal interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) levels in the gastric mucosa were investigated. Results: Significant inflammatory mucosal changes were observed in the H. pylori infection groups. The EGCG and triple-drug treatments significantly decreased the severity of gastritis in the antrum and the corpus. The mRNA levels of IL-1 beta, TNF-alpha, COX-2 and iNOS were increased in the H. pylori-infected gastric mucosa and obviously lower in the EGCG group than in the H. pylori-infection groups. Conclusions: The activations of IL-1 beta, TNF-alpha, COX-2 and iNOS were essential for H. pylori-induced gastritis in Mongolian gerbils. EGCG exhibited anti-inflammatory effects that might be mediated through the inhibitions of IL-1 beta, TNF-alpha, COX-2 and iNOS in the gerbil model of H. pylori-induced inflammation.