Aim: To investigate the effect of geranylgeranylacetone (GGA) on the progres-sion of atrophic gastritis in rats and its potential mechanism. Methods: Atrophic gastritis was induced in Sprague-Dawley rats with 0.1% ammonia solution, 60% ethanol, and 20 mmol/L deoxycholic acid for 24 weeks. Accompanied by the induction of atrophic gastritis, 200 mg/kg GGA was administered by oral gavage for 8 weeks (weeks 17-24). The histological changes in gastric mucosa were quantitated by the index of inflammation, the gastric mucosal thickness, and the amount of glands of 1 mm horizontal length in antrum. Endogenous heat shock protein (HSP)70 levels and distribution were determined by immunoblotting and immunohistochemistry in gastric mucosa. Results: GGA alleviated the pathologi-cal progression of atrophic gastritis with inflammation relief (inflammation index: 1.40 in the GGA group and 1.65 in the atrophic gastritis group) and glandular restoration (ucosal thickness and quantity of glands: 194.3 μm and 38.7 mm in the GGA group; 123.3 μm and 32.7 mm in the atrophic gastritis group; P<0.05). GGA significantly induced HSP70 synthesis (P<0.05). Moreover, quercetin, an inhibitor of HSP70 expression, aggravated the infiltration of inflammatory cells and glandular loss in the antrum. Conclusion: GGA prevented the progression of atrophic gastritis in rats via the induction of HSP70 expression.