Objective: Chronic appendicitis (CA) is a diagnosis characterized by long-standing right lower quadrant pain. We analyzed clinical, morphological, and immunohistochemical studies of the appendix to confirm the adequacy of surgery for CA in children with chronic right lower quadrant pain. Patients and Methods: We carried out comparative studies of clinical presentations and results of morphological and immunohistochemical studies of remote appendicitis in 55 children with chronic recurrent lower quadrant pain (CRLQP). Results: Morphological and immunohistochemical studies revealed three types of changes in the appendix. Type 1 (n = 21) - chronic inflammation. Inflammatory leukocyte infiltration was localized within the mucous membrane of the appendix. An immunohistochemical study revealed a significant (P < .01) increase in the expression of CD106 (vascular cell adhesion molecule 1) and in the number of matrix metalloproteinase 9 (MMP-9) positive cells. Type 2 (n = 20) - lymphoid hyperplasia. Morphological changes were characterized by lymphoid infiltration of the mucosa and submucosa of the appendix. Immunological changes were characterized by an increase (P < .01) in the expression and number of MMP-9, expression of CD106 positive cells, an increase in the expression of collagen IIIα in combination with a decrease in the expression and number of positive vascular endothelial growth factor (VEGF) and vasoactive intestinal peptide cells. Type 3 (n = 12) - catarrhal inflammation. Morphological changes were characterized by impaired blood circulation only in the mucous membrane, without destructive or inflammatory changes. Immunological changes were characterized by an increase (P < .01) in the expression and number of VEGF-positive cells, which may indicate a response to local hypoxia of the appendix and explain neovascularization in a chronic condition. The abdominal syndrome after appendectomy was noted to disappear in 89% of patients. The established changes in remote appendicitis, other than acute inflammation, make it possible to consider reasonable appendectomy a way of treating CRLQP in children. Conclusions: We have identified immunohistochemical and morphological changes pointing to autoimmune and vascular mechanisms of appendix damage in children with CRLQP. Laparoscopic appendectomy helps to eliminate abdominal pain in most CA patients. © Copyright 2021, Mary Ann Liebert, Inc., publishers 2021.