【Abstract】Objective To examine the role of glucocorticoid receptor (GR) in regulation of lipopolysaccharide (LPS)-induced lung injury. Methods 84 mail Sprague-Dawley rats(180-230)g were divided into five groups randomly: control group (n=6), LPS group (n=6 each), Dex+LPS group (n=6 each), RU486 group (n=6) and RU486+Dex+LPS group (n=6 each). All the groups were subjected into 1h, 3h, 6h and 12h time point after LPS administration, except of control group and RU486 group. We detected the concentration of albumin in bronchoalveolar lavage fluids (BALF), lung index (LI), the histopathologic changes of lung tissues. Apoptotic cells were stained by the terminal deoxynucleotidyi transferase-mediate dUTP nick-end labeling (TUNEL) technique. Average TUNEL-positive pneumocytes (apoptosis index, AI) were counted on 10 fields (×400) per specimen. Further, we explore the activation of p38MAPK and the expression in lung tissue. Results BALF protein content, LI, AI significantly increased at 6h after LPS administration (P<0.05). Pulmonary H-E stain showed edma (both interstitial and alveolar) and nutrophil infiltration in alveolar tissue. Alveolar spaces were narrowed and neutrophils exuded. In animals with Dexamethasone (Dex) administration, the albumin leakage and LI was significantly attenuated with protection of tissue damage. Also, the apoptosis of alveolar wall cells was reduced by Dex treatment, while all the protective effects of Dex might be cancelled by GR antagonist (RU486). Western blot analysis showed dexamethasone inhibited the phosphorylation of p38MAPK in lung tissues and the protective effects might be mediated by GR. Conclusion: GR plays an essential role in regulation of LPS-induced ALI. Anti-apoptosis effects of hormone-activated GR may be mediated by inhibition of p38 MAPK phosphorylation/activation.