Abstract: Objective To determine the therapeutic value and associated mechanism of diammonium glycyrrhizinate (DG) on the expression of AQP-5 in lipapolysacchairides (LPS)-induced acute lung injury in mice. Methods Thirty male BALB/c mice were randomly divided into three groups equally: Control, LPS+DG and LPS. HE staining and lung injury score system were used to evaluate the pathological changes in the lung tissues. Wet to dry ratio (W/D) was used to measure the degree of lung edema. RT-PCR and Western blot were obtained to measure AQP-5 expression. Total NF-κB p65 and phospho-NF-κB p65 (p-NF-κB p65) were evaluated by Western blot. Results After 3 days of LPS intratracheal injection, severe pathological changes, increased W/D, down-regulated AQP-5 expression and increased p-NF-κB p65/total NF-κB p65 were observed. Compared with mice in the LPS group, mice in the LPS+DG group had more significantly ameliorated pathological changes and increased W/D, up-regulated AQP-5 expression, and reduced p-NF-κB p65/total NF-κB p65. Conclusion DG up-regulates AQP-5 in vivo, possibly resulting from inactivation of NF-κB.