Objective: We recently reported in growing rats chronically intoxicated with lead (Pb) and exposed to the stress of intermittent hypobaric hypoxia (IHH) deleterious effects on periodontal and dental tissues that could be due to a greater vulnerability of them to inflammatory processes (1). Periodontitis is characterized by inflammation of the supporting tissues of the teeth and periodontal pocket formation that result in alveolar bone resorption and soft tissue attachment loss. It has been suggested that the submandibular gland functions are a key regulatory organ in the oral neuroimmunoregulatory network (2). The aim of the present study was to establish in the same rat model, the macroscopic, biochemical and histological parameters consistent with a periodontal disease. Methods: Sixty female Wistar growing rats were randomly divided into 4 groups: C (control); Pb (intoxicated with 1000 ppm of lead acetate in drinking water for 90 d); IHH (exposed to 506 mbar, 18 h/d during 90 d in a simulated high altitude chamber) and Pb-IHH (both treatments together). At the end of the experimental period the submandibular glands (SMG) were extracted to measure TBA-RS, as a marker of cellular oxidative stress and prostaglandin E2 (PGE2) known to be increased under oral inflammatory conditions (3). Hemimandibles were resected to assess bone loss by measuring the distance between the cemento-enamel junction and the alveolar bone crest of the first molars roots and to perform histomorphometric studies in decalcified sections stained with H&E. Values are means ± SD, compared by ANOVA followed by Student-Newman-Keuls tests. Results: Hypoxia enhanced TBA-RS content in SMG being the increase even greater in PbIHH group (C: 11.11±0.73; Pb: 11.59±0.46; IHH: 13.89±0.88 and PbIHH: 15.49±0.70 nmol/mg SMG wet weight, p<0.01). Both treatments enhanced PGE2 content in the SMG, showing an additive effect in the PbIHH group (C: 332.69±123.99; Pb: 476.19±135.02; IHH: 546.24±122.42 and PbIHH: 1165.09±204.51, p<0.01). IHH showed significantly higher buccal alveolar bone loss vs their control but surprisingly it was lower in the PbIHH group. Conclusion: Treatments enhanced some systemic and oral tissues inflammatory parameters, which could lead to a periodontal disease in individuals living in lead contaminated high altitude areas. UBACyT 20020090200013.