Objective To investigate the protective effects and mechanisms of rosiglitazone on lung injury in severe acute pancreatitis (SAP). Methods Seventy-two SD rats were randomized into three groups: sham operation (SO) group, SAP group and rosiglitazone-pretreated group. The model of SAP was induced by retrograde injection of 5%sodium tauro-cholate into the bili-pancreatic duct in SD rats. Rats of rosiglitazone-pretreated group were given 10 mg/kg rosiglitazone in-traperitoneally 30 min before inducing SAP. The amylase plasma levels, levels of TNF-αand p(O2), the myeloperoxidase (MPO) and the wet/dry ratio of lung tissue were measured. The expression of NF-κB in pulmonary tissues was assayed by im-munohistochemistry. The expressions of TNF-αmRNA and intercellular adhesion molecule 1 (ICAM-1) mRNA in pulmo-nary tissues were detected by reverse transcript PCR (RT-PCR). The histopathological changes of pulmonary tissues were evaluated. Results Compared with SO group, the plasma levels of amylase and TNF-α, the intrapulmonary MPO were sig-nificantly increased in SAP group (P＜0.05). The expression levels of NF-κB, TNF-αmRNA and ICAM-1 mRNA in lung tissue were also significantly increased in SAP group (P＜0.01). There were significantly lower levels of the above indicator in rosiglitazone-pretreated group than those of SAP group (P＜0.05). Compared with SO group, the lung wet/dryratio was sig-nificantly higher at 6 h and 12 h in SAP group (P＜0.05). The values of lung wet/dry ratio were significantly lower at 6 h and 12 h in rosiglitazone-pretreated group than those of SAP group (P＜0.05). The lung tissue damage was significantly reduced. The level of p(O2)was significantly decreased in SAP group than that of SO group (P＜0.05). The level of p(O2)was signifi-cantly increased at 6 h and 12 h in rosiglitazone pretreated group than that of SAP group (P＜0.05). Conclusion Rosigli-tazone might have protective effects on SAP-related lung injury by inhibiting NF-κB and decreasing the production of TNF-αand ICAM-1in the lung tissues.