Sinus congestion resultant of allergic rhinosinusitis is associated with development and worsening of asthma and can result in difficulty breathing, headaches, and missed days of school and work. Quantification of sinus congestion is important in the understanding of allergic rhinosinusitis, and the development of new drugs for its treatment. Non-invasive micro-computed tomography (CT) was investigated in a Guinea pig model of allergic rhinosinusitis to determine if it could be used to accurately determine the degree of sinus congestion and resolution with anti-inflammatory drug administration. Three-dimensional sinus airspace volume, 2-dimensional sinus width, sinus image airspace area, and sinus image sinus perimeter, were measured in Guinea pigs administered ragweed pollen (RWP), intranasally (i.n.), followed by administration of fluticasone, i.n. To determine their relative accuracy in assessing sinus congestion, the micro-CT image results were compared with the "gold-standard" method of sinus fluid fill-volume (SFFV) measurements. As measured by SFFV method, RWP increased sinus congestion in a RWP concentration-dependent fashion, approaching near-total sinus blockage with concentrations ≥22 µg RWP. At this level of congestion, fluticasone (25-100 µg) progressively decreased sinus congestion in a concentration-dependent fashion. The non-invasive micro-CT methods were found to accurately determine the amount of sinus congestion and resolution, with patterns of increases and decreases of congestion that were nearly identical to the SFFV method. We conclude that non-invasive micro-CT measurements of allergic sinus congestion can be useful as an investigative tool in the assessment of congestion intensity and the development of new drug therapies for its treatment.