Disturbances in pulmonary vascular reactivity are important early components of inflammatory lung disease. The present study aims to extrapolate the relationship between the inflammatory response and changes in pulmonary vascular response and to investigate the potential protective effect of HO-1 against inflammation-induced disturbance in pulmonary vascular response. A number of techniques were used to achieve these goals including: the isolated artery technique, real time recording, confocal fluorescence microscopy, HO 1 immunoblotting, immunofluorescence techniques, HO activity assay and flow cytometry. We have shown, for the first time, that induction of HO-1 protein and activity was associated with protection against cytokine induced dysfunction of pulmonary artery relaxation and that this protection was mediated by modulation of NO production in arterial tissue. These findings suggest upregulation of HO-1 as a novel potential therapy in the management of vascular disturbances associated with inflammatory lung disease.