Abstract: AIM: To observe the role of insulin in the prevention and treatment of lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rabbits and to further explore the underlying mechanism by which insulin exerts protective effects on LPS-induced ALI. METHODS: New Zealand white rabbits were divided randomly into four groups: saline control group, LPS group, insulin+LPS group and LPS+insulin group. The animal model of ALI was established by intratracheal administration of LPS 0.5 mg/(ml·kg). Microinjection pump was used to inject solution through ear-edge vein. NS group and LPS group received normal saline for 4 hours. Insulin+LPS group received insulin mixed liquor 0.5 hour before intratracheal administration of instilled LPS. LPS+insulin group received insulin mixed liquor 0.5 hour after intratracheal administration of instilled LPS. The insulin mixed liquor was given continuously for 4 hours. During that period, the mean carotid arterial pressure (mCAP), the glucose of venous blood and the K+ concentration of arterial blood were monitored. After experiment, the histological changes of lungs were observed and the left lung wet-to-dry (W/D) weight ratios were evaluated. SOD and MDA in lung homogenate were also measured. RESULITS: mCAP declined persistently (8.09±1.12) kPa and the contents of glucose of venous blood persistently ascended (12.8±5.6) mmol/L in LPS group. But insulin kept mCAP at higher levels (P<0.05). Histological studied showed that there were congestion, edema and the sequestration of inflammatory cells in lung tissues in LPS group, but lung injury was significantly alleviated in insulin+LPS and LPS+insulin groups. The W/D and the content of MDA highly increased and the activity of SOD decreased (P<0.05) in LPS group. Insulin inhibited all the increased parameters and upgraded the activity of SOD (P<0.05). CONCLUSION: Insulin prevents and relieves LPS-induced rabbit ALI, which may be related with the inhibition of oxidative stress.