Objective: To investigate the changes of the number of mast cell and IL-5 expression in gastric mucosa of children with eosinophilic gastroenteritis (EG) and their clinical significance. Methods: Twenty children including 16 male cases and 4 female cases aged (6.34±4.51) years old were diagnosed as EG at the Department of Gastroenterology of Children’s Hospital affiliated to Nanjing Medical University from July 2015 to August 2016. Twenty children including 15 male cases and 5 female cases aged (5.46±3.27) years old were divided into the control groups according to the number of eosinophils (EOS) in peripheral blood and gastric mucosa tissues, total immunoglobulin E (IgE) levels in peripheral blood. The number of EOS in peripheral blood was counted and total IgE levels were measured in both groups and gastric mucosal tissues were taken under endoscopy. Then we carried out HE staining, toluidine blue staining so as to count the number of EOS and Mast cells (MC) in gastric mucosal tissues. IL-5 mRNA expression in gastric mucosa was detected by fluorescence quantitative PCR. Results: The number of EOS and level of total IgE in peripheral blood of EG patients were significantly higher than those in control groups (P<0.05). The number of EOS and MC in gastric mucosa in EG groups was increased compared with the control groups (P<0.05). The expression of IL-5 mRNA in gastric mucosa in EG groups was increased than that in the control groups. Conclusion: The increased number of MC in the gastric mucosa may lead to the increased release of IL-5, which can cause the accumulation and activation of EOS and toxic factors in the gastric mucosa leading to the damage of mucosal tissue.