This study aimed to investigate the association of inflammatory changes of upper and lower airways in a rabbit model of acute rhinosinusitis. The study included six adult albino rabbits. The sinuses of one animal were injected with saline solution and the animal was served as sham control. Other animals were implanted with intranasal S. aureus soaked-absorbable gelatin sponge. Acute rhinosinusitis was induced and subjects were sacrificed at the end of the second week. Tissue samples from all levels of the airway were obtained. They were evaluated for the presence of inflammatory changes histologically. A scoring system for airway inflammation was used for quantitative assessment of the degree of inflammation. Structural changes in the epithelial and stromal layers of the upper and lower airway structures were analyzed, as well. The animal of which the sinuses were injected with saline solution developed neither acute rhinosinusitis nor lower airway inflammation. In contrast, the animals in which acute rhinosinusitis was induced demonstrated significant upper and lower airway inflammation histologically. Inflammatory changes ranged from engorgement of blood vessels and polymorphonuclear cell proliferation within the capillaries, in the perivascular tissue of the epithelium or in the lamina propria and to epithelial disruption. Nasal airway inflammation scores (2.86 +/- 1.81) were significantly higher than lower airway scores (1.36 +/- 0.77), (P < 0.01). We obtained a generalized mucosal inflammatory response against localized bacterial inflammation in a rabbit model of acute rhinosinusitis, confirming the suggestion of 'one airway-one disease' from a bacterial infection point of view.