Background: Although a juvenile polyp is the commonest pediatric polyp, little is known regarding its pathogenesis. Objective: We aimed to study the role of eosinophils and platelet-derived growth factor receptor A (PDGFRA) expression in juvenile polyps. This could help in understanding the possible mechanism of polyp formation. Material and methods: This was a retrospective study that included 63 cases of juvenile polyps that were divided into three groups according to the number of polyps. Peripheral and tissue eosinophilia was evaluated. An immunohistochemical study of mothers against decapentaplegic homolog 4 (SMAD4) and PDGFRA was conducted. Results: The majority (82.5%) of the juvenile polyps were solitary, 11.1% were multiple, and 6.4% of them were cases of juvenile polyposis syndrome. There was an increased number of blood eosinophils (a median value of 2 × 10³ cells/µL) and tissue eosinophils (a median value of 30/HPF). In addition, PDGFRA was overexpressed in 66.7% of cases. The expression of PDGFRA was significantly associated with tissue eosinophilia (p = 0.008). Tissue eosinophilia and PDGRA overexpression were significantly observed in patients with maintained SMAD4 expression. Conclusions: Tissue eosinophilia and PDGFRA overexpression were observed in majority of juvenile polyp cases. Juvenile polyps could share histopathological and molecular similarity to inflammatory fibroid polyp. The pathogenesis of juvenile polyp could be influenced by allergic or neoplastic factors.