Abstract: Objective To investigate whether sulforaphane (SF) has protective effects on acute lung injury (ALI) in mice through a mechanism of reducing inflammation and oxidative stress by up regulation of transcription factor NF-E2 related factor 2 (Nrf2). Methods Thirty-six healthy mice were divided into 4 groups: the control group (group C), the ALI group, the SF vehicle group (group vehicle) and the SF group. SF group was intraperitoneally injected with SF twice a day for three days, while vehicle group was injected with vehicle. On the fourth day, C group was intraperitoneally injected with normal saline, while the other groups were injected with equal volume of LPS to induce acute lung injury. The levels of IL-6 and TNF-α in serum was measured by ELISA method 6 hours after the injection of LPS or normal saline. The mice were then sacrificed, and the pathological changes in lung tissue were observed under light microscope to get the lung injury scores. The lung W/D weight ratio of the mice in each group was calculated, and the expression of Nrf2 nucleoprotein in lung tissue was measured. The activity of MPO, iNOS and SOD was measured by a kit. Results Compared with the C group, the lung injury score, the levels of IL-6, TNF-α, MPO, iNOS and Nrf2 protein was increased, while the ratio of W/D weight and the level of SOD was decreased significantly in ALI and vehicle group (all P<0.05). The increased Nrf2 expression reduced the lung injury score, the levels of IL-6, TNF-α, MPO and iNOS, while increased the level of SOD, the W/D weight ratio in SF group (all P<0.05), compared with the ALI group, while in vehicle group all had no significant difference compared with the ALI group (all P>0.05). Conclusion SF can up regulate the expression of Nrf2. The up regulation of Nrf2 can mitigate the severity of acute lung injury induced by LPS, reduce the concentration of proinflammatory mediators in serum and the oxidative stress index in the tissues. Our data suggested that the Nrf2 transcription factor exerted its protection from the damage in ALI model through a mechanism of reducing inflammation and oxidative stress.