Chronic diseases of lifestyle (CDL), the most common chronic group of diseases, which share the similar risk factors of unhealthy lifestyle, have become most recognized as a serious trigger in the genesis of oesophageal mucosa (OEM) injury. Non-erosive lesions (NEOL) related to CDL are found more frequently than erosive/ulcer OEM lesions in patients. Therefore, developing a physiologically relevant animal model of NEOL remains an urgent priority. One of triggers of CDL is postprandial hyperglycemia (PHG), which characterized by disbalance in pro- and anti-inflammatory factors [1]. The role of H2S has been suggested to contribute in endothelial dysfunction and inflammation [2, 3]. The present study was designed to set up a model of NEOL in rodents related to CDL with modification of biosynthesis of H2S to understand mechanisms of NEOL under s long-term PHG. Rats (male, 180-230g, n=50) were used with without/with altering H2S production via cystathionine γ-lyase (CSE) inhibitor, DL-propargylglycine (PAG, 25 mg/kg/day i.p.), cystathionine-β-synthetasa (CBS) inhibitor, O-carboxymethylhydroxylamine (CHH, 3 mmol/L/day i.p.), or H2S donor NaHS (100 mlmol/kg/day, i.p.) after 28 days of PHG (Kozar, 2011). Rats were anaesthetized with ketamine (60 mg kg-1 i.m.). NEOL were determined via histological score index (HSI, EsoHisto guidelines, 2011) and lectinhistochemistry via mannose (Man)-containing specific (α-DMan) and fucose (Fuc)-rich Fuc-α1 glycoconjugates in OEM; IL-10, IL-17 via ELISA. Values are means ± S.E.M., compared by ANOVA. PHG-associated OEM injury in rats with inhibition of H2S via CSE, CBS developed submucosal oedema and leukocytes infiltration, including formation of destructive lesions in muscular lamina as well as basal cell hyperplasia, rise of HIS in 4-fold vs control (p<0,05). Dynamic changes in OEM glycoconjugates during PHG were with highest α-DMan labeling in vascular endothelium, for Fuc-α1 in epithelial layer vs our previous data about sialoglycans [4]. Over-expression of IL-17 showed a significant increase during CHH then PAG pre-treatment 2,2±0,2 vs 1,1±0,1 pg/ml (p<0,05), respectively. Moreover, increased IL-10 and decreased IL-17 were recorded after NaHS administration. Thus, our study of induction of PHG, CDL-related condition, with blocking activity of bioregulators of H2S provided a novel experimental model with NEOL and induction of low-grade inflammation that can potentially be useful in preclinical study. Modification of H2S endogenic biosynthesis in rats helps in identifying the physiologic impact of H2S as a molecular mediator associated with endothelial dysfunction during NEOL. This study suggests an important role for αDMan and Fuc-α1 in pro-inflammatory signaling network cell for OEM survive.