Inflammation and endothelial dysfunction are central to esophageal barrier impairment and starting point for abnormal restitutio ad integrum and neoplastic processes [1]. WHO indicated that risk for premalignant Barrett’s esophagus increased with chronic esophagitis. Glycoproteins incorporated into plasma membrane are essential for the initiation and regulation of immune responses and effective tool of representing injury-cell-associated immunogenicity in vivo. We hypothesized that α-d-mannose (αdMan) and sialic acid (NEU5AC) containing glycoconjugates interacted at a defence/receptor level in much the same fashion as pro-inflammatory cytokine in esophageal integrity. We therefore evaluated the receptor αdMan and NEU5AC profiles and inflammatory signaling contributed for the esophageal phenotype of integrity and cytoprotection without/with L-tryptophan (L-Try) and melatonin (MT)-pretreatment, which enhancing esophageal barrier functions. Erosive esophagitis (EES) by perfusion solution of 0,25 N HCl & pepsin and non-erosive esophagitis (NES) by Takagi, 1964 were induced in rats without/with L-Try (200 mg/kg per os) and MT (20 mg/kg/ip) treatment which were anaesthetized with intramuscular administration of ketamine (60 mg kg-1); after 24 h of injury rats were killing and the healing of esophageal lesions and estimation of esophageal mucosa destruction, inflammation and hyperplasia via histological score index (HSI), αdMan, NEU5AC expression by lectinhistochemistry; IL-1β, TNFα by ELISA. Acidic perfusion induced topical EES and HSI was 2,5-folds time more than with MT treatment; NES was with constantly increased HSI in 150% in compare to MT treated rats showing the same effect as in model of acidic EES. Dynamic changes in esophageal mucosa glycobiology features with higher intensity NEU5AC labeling in EES vs NES, and highest αdMan labeling was in endothelium of vessels in NES, indicated ion endothelial dysfuction in physiopathogenesis of non-erosive and erosive esophagitis. Basal IL-1β was 24,16±0,30 pg/ml, TNFα – 1,05±0,11 pg/ml. Induction of EES led to increased IL-1β to 55,35 ± 7,88 pg/ml, TNFα – 5,56 ± 0,55 pg/ml (p <0,05). In non-erosive lesions IL-1β increased at 38,7 %, TNFα – 65,6% relatively to control (p <0,05). Potent angiotropic Mel and L-Try effects were estimated on esophageal cytoprotection and repair via decreasing αdMan expression in esophageal vascular walls. Anti-inflammatory effect of L-Try was less then MT that caused decrease of IL-1β to 21,8%, TNFα – 35,1% compared to control. This study suggests an important role for αdMan and NEU5AC in EES and NES cell survival. Novel findings relating to high αdMan expression in endothelium and NEU5AC in compromised esophageal mucosa integrity might be associated with the development low grade inflammation and metaplasia.