Recent investigations of chronic sinusitis that is "recalcitrant" to traditional medical and surgical therapy indicate that gram negative bacteria are frequently involved, most commonly Pseudomonas aeruginosa. Analysis of infection-induced histopathologic changes in the underlying sinus mucosa may provide important insight into the recalcitrant nature of these infections. Therefore, the aim of this investigation is to experimentally induce sinus infection in the rabbit with Pseudomonas aeruginosa, a bacterium commonly associated with "recalcitrant sinusitis," and evaluate the histopathologic findings. A unilateral maxillary sinusitis was induced in 33 New Zealand white rabbits. Histologic analysis at 4, 14, 21, and 28 days revealed a moderate inflammation that persisted throughout the study period. Initial changes included edema, loss of submucosal glands, and ulceration. Fibroplasia and bone remodeling were evident throughout the study. Epithelial plaque formation occurred early in the infection, whereas goblet cell formation was a later change. Experimental sinusitis induced by Pseudomonas aeruginosa causes an intense transmucosal injury. The histopathologic injury and response to Pseudomonas aeruginosa appears to be more intense than that noted on previous investigations of experimental sinusitis using other bacteria. The significant histopathologic changes noted could explain the recalcitrant nature of gram negative sinusitis observed clinically in patients.