Changes in the levels of serum oxidative stress indexes, gastrointestinal hormones and inflammatory factors in children with different severity of reflux esophagitis (RE) were detected. Sixty child patients diagnosed with gastroesophageal reflux disease (GERD) via gastroscopy were selected and divided into non-erosive reflux disease group (NERD group, n=12) and RE group (n=48) according to whether there was esophageal mucosal injury. In RE group, the patients were further divided into grade I RE group (n=15), grade II RE group (n=18) and grade III RE group (n=15) based on the severity of mucosal injury. None of the child patients took PPI and domperidone within 2 weeks before enrollment. The content of malondialdehyde (MDA) and total superoxide dismutase (T-SOD) in the esophageal mucosa was detected. The changes in the levels of serum vasoactive intestinal peptide (VIP), motilin, interleukin-1β (IL-1β), IL-8 and tumor necrosis factor-α (TNF-α) were determined. The DeMeester score was the highest in grade III RE group, followed by grade II RE group, grade I RE group and NERD group (P<0.05). The content of MDA in the esophageal mucosa was higher in RE group than that in NERD group, and the T-SOD activity declined with the increased severity of injury (P<0.05). In the three RE groups, the level of plasma VIP was significantly higher, while the motilin level was remarkably lower than those in NERD group (P<0.05). With the increased severity of disease, the expression levels of serum IL-1β, IL-8 and TNF-α in RE group were gradually raised (P<0.05). RE patients have strong oxidative stress and inflammatory response, an increased level of serum VIP, a regulator of gastrointestinal motility, and a decreased level of motilin. Controlling the changes in the above factors using effective treatment means can improve the development of GERD.