Objective Abdominal aortic aneurysm rupture is associated with a systemic inflammatory response syndrome and acute lung injury. Using a selective inducible nitric oxide synthase (iNOS) inhibitor, N 6-(iminoethyl)-lysine (L-NIL), we explored the role of iNOS in the early pro-inflammatory signaling and acute lung injury in experimental abdominal aortic aneurysm rupture. Materials and methods Anesthetized rats were randomized to sham control or shock and clamp (s + c) groups, which underwent one hour of hemorrhagic shock, followed by 45 minutes of supramesenteric aortic clamping, and then two hours resuscitated reperfusion. Animals in s + c were randomized to receive intravenous L-NIL at 50 μg/kg/h or saline at the start of reperfusion. Pulmonary permeability to 125I-labeled albumin, myeloperoxidase (MPO) activity, cytokine levels, and semi-quantitative RT-PCR for mRNA were indicators of microvascular permeability, leuco-sequestration, and pro-inflammatory signaling, respectively. Results Lung permeability index were significantly increased in s + c compared to sham (4.43 ± 0.96 versus 1.30 ± 0.17, P < 0.01), and attenuated by L-NIL treatment (2.14 ± 0.70, P < 0.05). Lung tissue MPO activity was significantly increased in s + c compared to sham (2.80 ± 0.32 versus 1.03 ± 0.29, P < 0.002), and attenuated by L-NIL treatment (1.50 ± 0.20, P < 0.007). Lung tissue iNOS activity was significantly increased in s + c compared to sham animals ( P < 0.05), and attenuated by L-NIL treatment ( P < 0.05). Lung tissue iNOS mRNA was upregulated 8-fold in s + c compared to sham ( P < 0.05). Data represents mean ± standard error mean, comparisons with ANOVA. Conclusions These data suggest that in our model of ruptured abdominal aortic aneurysm iNOS plays a crucial role in reperfusion lung injury. Selective inhibition of iNOS during early reperfusion prevents neutrophil mediated acute lung injury.