Olfaction is an essential sensory modality; it supports physiological functions such as feeding and reproduction. The first step in olfactory perception takes place at the peripheral level in a neuroepithelium named the olfactory mucosa (OM), through activation of olfactory sensory neurons (OSN). We have recently demonstrated that Wistar rats subjected to chronic variable stress exhibited deficiencies in OM function, possibly through sustained glucocorticoid secretion (Raynaud et al., 2015, Behavioural Brain Research, 291, 36-45)). The aim of this study was to test whether glucocorticoid hormones can directly affect olfactory function. Following detection of the glucocorticoid receptor (GR) in the OM, we hypothesised that: (1) GR action could be pharmacologically regulated in vitro; (2) acute in vivo (2mg/kg ip, 6h) injection of synthetic glucocorticoid (dexamethasone) would affect OM gene expression and electrophysiological properties; (3) dexamethasone would alter rat behaviour in response to olfactory stimulation. In contrast with published data, GR was not expressed in OSN but in the glial-like Olfactory Ensheathing Cells (OEC). In OEC primary cultures, expression of a GR activation marker gene (SGK1) was increased by dexamethasone, but repressed with the antagonist RU486. In vivo, SGK1 and other GR-regulated transcripts were affected by dexamethasone. This was accompanied by up to 30%reduction in ElectroOlfactoGram signal amplitude in response to odorants. Dexamethasone did not affect rat behaviour in an open field, but their reactivity was increased in an olfactory-based habituation-dishabituation task. The first step of olfactory detection is sensitive to glucocorticoid hormones; we are further investigating the biological significance of this phenomenon.