Background/Aims: To determine whether the expression of tight junction proteins (TJPs) differs depending on the subtype of functional dyspepsia (FD) and sex. Methods: Control (n = 95) and FD (n = 165) groups based on Rome III criteria were prospectively enrolled. Gastric mucosal mRNA expression levels of various TJPs (claudins [CLDN] 1, 2, and 4; zonula occludens-1; occludin [OCLN]) were assessed by reverse transcription polymerase chain reaction. Western blot was performed to determine the levels of various TJPs. Helicobacter pylori infection status was evaluated by histology, rapid urease test, and culture. Questionnaires were analyzed. Results: In all groups irrespective of H. pylori , FD group showed significantly higher CLDN2 mRNA levels than control group (P = 0.048). The level of CLDN4 mRNA expression was significantly lower in female FD group than in male FD group (P = 0.018). In H. pylori uninfected subjects, the level of CLDN1 mRNA expression in female FD group was significantly lower than that of male FD group (P = 0.014). The level of CLDN2 mRNA expression was significantly higher in the male postprandial distress syndrome (P = 0.001) and male epigastric pain syndrome (P = 0.023) groups than in the male control group. In Western blot analysis, the expression of OCLN was significantly elevated 48 hour after the culture with H. pylori strain 43504. Conclusions H. pylori can affect a variety of TJPs, particularly claudin-4 and occludin. Claudin-2 is thought to be involved in FD irrespective of H. pylori status, especially in the pathophysiology of male FD.