To investigate the role of transforming growth factor beta1 (TGFbeta1) in the development of Helicobacter pylori (H.pylori)-associated non-metaplastic atrophic gastritis.The expressions of TGFbeta1, CD68 and smooth muscle actin(SMA) were detected immunohistochemically in 10 patients with mild non-atrophic gastritis, 30 patients with mild non-metaplastic atrophic gastritis, and 32 patients with severe non-metaplastic atrophic gastritis having H.pylori infecion. Meanwhile, three cases of mild non-atrophic gastritis and 4 cases of severe non-metaplastic atrophic gastritis were observed with electron microscope.The count of TGFbeta1 positive cells per high-power field (HPF) in severe non-metaplastic atrophic gastritis group (53 +/- 22) was significantly higher than that in mild non-atrophic gastritis group(22+/-9/HPF) and mild non-atrophic gastritis group(0-3/HPF, P<0.01). The count of CD68 positive cells in severe non-metaplastic atrophic gastritis group (23+/-7/HPF) was significantly higher than that in mild non-atrophic gastritis group (13+/-6/HPF) and mild non-atrophic gastritis group(0-3/HPF, P<0.01). Correlation analysis showed that the expressions of TGFbeta1 and CD68 had a moderate correlation in each group (r=0.634, P<0.01; r=0.699, P<0.01). Compared with mild non-atrophic gastritis, SMA-positive myofibroblasts and smooth muscle cells in the lamina propria increased in mild and severe non-metaplastic atrophic gastritis. Ultrastructurally, the proliferation of fibroblasts in gastric lamina propria was observed in mild non-atrophic gastritis, while the proliferation of fibroblasts and presence of myofibroblasts could be observed in mild non-metaplastic atrophic gastritis, and there was a parallel phenomenon between myofibroblasts and fibroblasts, as well as smooth muscle cells.Our findings indicate that TGFbeta1 expression increases with severity of H.pylori- associated non-metaplastic atrophic gastritis, suggesting that TGFbeta1 might play an important role in the development of non-metaplastic atrophic gastritis.