Objective To investigate the modulatory effects of glycyrrhizin (GL) on the expressions of nu-clear factor kappa B (NF-κB), glucocorticoid receptor (GR) and cytokines in serum, and to explore the protective mechanism of GL in acute lung injury (ALI) induced by lipopolysaecharide (LPS). Method Twenty-four male Sprague-Dawley rats were randomly(random number) divided into three groups (n = 8 in each) : normal group, ALI group and GL treatment group. Rats in the ALI group and GL treatment group were administered with LPS (5 mg/kg) intravenously. In GL treatment group, rats were treated with GL (20 mg/kg) one hour before LPS injec-tion. The animals were sacrificed 4 hours after injection of LPS, and then the lung wewt/dry ratio and PaO_2 were measured, the histopathology of lung injury was observed under light microscope, the expressions of NF-κB mRNA and GR mRNA in lung tissues were detected by using RT-PCR, and the levels of NF-κB protein and GR protein were determined by using Western blot. The levels of TNF-α and IL-10 in serum were observed by using ELISA.Data were analyzed with SPSS version 13.0 software, and means were compared with analysis of variance and Stu-dent-Newman-Keuls test. Results (1) TNF-α levels in normal group, ALI group and GL treatment group were (43.96±7.57), (153.68±20.42), and (87.23±7.52) ng/L, respectively, and IL-10 levels were (24.72±8.03), (42.48±6.81) and (58.33±9.62) ng/L, respectively (F = 183.70, all P <0.01). (2) NF-κB mRNA expressions in normal group, ALI group and GL treatment group were (0.432±0.085), (3.414±0.521) and (1.894±0.272), respectively, and NF-κB protein levels were (45.6±7.3), (254.7±16.4)and (133.5 ±11.7) ng/L, respectively, and comparison between groups showed statistical significant (F = 187.82 and 1466.53, ALL P < 0.01). GR mRNA expressions in normal group, ALI group and GL treatment group were (0.434±0.013), (0.152±0.025) and (0.308±0.033), respectively, and GR protein levels were(54.6±6.5), (11.5±2.3)and (28.2±5.6) ng/L, respectively (F = 246.00 and 260.92, all P < 0.01). (3) Com-pared with normal group, infiltration of PMNs, capillary congestion and swelling were found in ALI group, and treatment with GL could attenuate the lung injury. Conclusions Glycyrrhizin has a protective effects on rats with ALI induced by LPS maybe through down-regulating the expressions of NF-κB mRNA and TNF-α mRNA, and up-regulating the expression of GR mRNA and level of IL-10 protein.