Rationale: O-GlcNAc, a post-translational modification closely linked to cell metabolism, has been suggested to play an important role in development. The suckling to weaning transition is associated with important change in metabolism but its impact on O-GlcNAc has never been explored. Objective: To evaluate O-GlcNAc level from birth to adulthood in different organs.Methods: Blood and tissue samples (heart, liver, kidney, lung, hind limb and brain) were harvested between 8 and 10 am at J0 (newbn), J12, J28 (before / after weaning) and J84 (adulthood) wistar rats to evaluate O-GlcNAc, GFAT (the rate limiting enzyme of hexosamine biosynthesis pathway), OGA (O-GlcNAcase) and OGT (O-GlcNAc transferase) levels.Results: O-GlcNAc level decreased progressively from J0 to J84 in the heart (5 fold) along with GFAT (50 fold) and OGT (10 fold) while the OGA main isoform is absent at J0. In the liver, O-GlcNAc levels were similar between J0 and J84 but OGT and GFAT decreased (2 and 3 fold respectively). O-GlcNAc proteomic study revealed different targets of interest.Conclusion: O-GlcNAc level decreases with ageing in the heart but not in the liver. Our results pinpoint to major and tissue-specific modulation in the expression and activity of the enzymes involved in the regulation of O-GlcNAcylation levels during post-natal development.