Objective To investigate protective effect of apocynin, the inhibitor of NADPH oxidase Ⅱ (NOX2), on lung injury induced by acute necrotic pancreatitis (ANP) in rat. Methods Forty SPF adult male Wistar rats were randomly divided into 4 groups: shame operation group (SO group, n=10), ANP model group (ANP group, n=12), apocynin treated group (APO group, n=10), and apocynin control group (APO-CON group, n=8). The ANP models were induced by the retrograde injection of 5% sodium taurocholate through the biliopancreatic duct in the ANP group and the APO group. The apocynin was injected at 30 min before the induction of ANP models in the APO group. The pancreas and duodenum of rats were just flipped and the apocynin and the 10% DMSO (2 mL/kg) were injected in the APO-CON group and SO group respectively. All the rats were sacrificed at 12 h after the operation. The blood samples were collected by the inferior vena cava puncture, and the levels of serum amylase and lipase were measured by the auto-chemistry analyzer. The lung tissues were harvested and the integrated optical densities (IODs) of the nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), and NOX2 were detected by the immunohistochemistry assay. The IODs of the myeloperoxidase (MPO), Toll like receptor 4 (TLR4), and CD68 were detected by the immunofluorescence assay. The concentration of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) were tested by the ELISA method. Results The levels of the serum amylase and lipase and the IODs of the NF-κB, TNF-α, NOX2, MPO, TLR4, CD68, and concentration of MDA of the lung tissues in the ANP group were significantly increased as compared with the SO group (P<0.05), these indices in the APO group were significantly decreased as compared with the ANP group (P<0.05). The SOD activity of the lung tissue in the ANP group was significantly decreased as compared with the SO group (P<0.05), which in the APO group was significantly increased as compared with the ANP group (P<0.05). Conclusion Apocynin can ameliorate lung injury induced by ANP through inhibiting activity of NOX2.