Geraniin, a typical ellagitannin isolated from Phyllanthusurinaria Linn, has been reported to have anti-inflammatory effect. The aim of the study is to investigate the therapeutic effects of geraniin on LPS-induced acute lung injury (ALI) in mice. The mice were intranasal adminisration of LPS for 12 h. Geraniin was intra-peritoneal injection 1 h after LPS treatment. The results showed that geraniin significantly attenuated LPS-induced pathological changes in the lung. Geraniin also inhibited LPS-induced macrophages and neutrophils infiltration in the lung. Geraniin significantly attenuated LPS-induced elevation of MPO level. LPS-induced TNF-α, IL-6 and IL-1β production were markedly suppressed by treatment of geraniin. Furthermore, geraniin inhibited NF-κB activation in LPS-induced ALI. In addition, geraniin was found to up-regulate the expression of Nrf2 and HO-1. In conclusion, these data suggested that geraniin had therapeutic effects in LPS-induced ALI by inhibiting NF-κB and activating Nrf2 signaling pathways.