PURPOSE: The purpose of this study was to assess the feasibility of inflammation detection in an antigen-induced arthritis model using fluorescent leukocytes and optical imaging. METHODS: Antigen-mediated monoarthritis was induced in the right knee of 12 Sprague-Dawley rats. Six rats remained untreated and six rats were treated with cortisone. All rats received ex vivo fluorescent-labeled rat leukocytes. Optical images of both knees were acquired before and at 5 min, 1 h, 4 h, and 24 h after cell injection. Images were evaluated qualitatively and quantitatively by calculating signal intensity ratios between the right arthritic (A) and contralateral normal (N) knee. A/N ratios were tested for significant differences between baseline values and values after cell injection using a paired t test as well as between the untreated and cortisone-treated group using an unpaired t test. Synovial specimens were processed and evaluated for labeled cells with fluorescence microscopy. RESULTS: At 4 h and 24 h p.i., the A/N ratios of untreated arthritic knees showed a significant signal increase compared with baseline values (p<0.05) and a significant difference compared with A/N ratios of cortisone-treated animals (p<0.05). Fluorescent microscopy confirmed the presence of labeled cells in the arthritic synovium. CONCLUSION: Inflammation in antigen-induced arthritis can be detected with ex vivo labeled allogenic leukocytes and optical imaging.