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Progress in developing novel rational treatments for rheumatoid arthritis (RA) critically depends on preclinical work in experimental animals. However, there is lack of insight into the most appropriate mode of noninvasive measurement of disease status in experimental RA. This study compared sonography with serum biomarkers in a rabbit model of RA.Six-month-old male New Zealand White rabbits were randomized into 2 groups: antigen-induced arthritis group (n = 25), which was subjected to ovalbumin immunization and intra-articular injection; and control group (n = 5). Pathologic changes in the knee joints were evaluated by sonography, and serum C-reactive protein, tumor necrosis factor TNF-α, and interleukin 1 were measured by enzyme-linked immunosorbent assay. Synovial pathologic scores were obtained by ultrasound-guided biopsy.A total of 23 rabbits (2 rabbits died before the end of the study) in the antigen-induced arthritis group and 5 rabbits in the control group completed the study. Sonographic scores for all rabbits were graded from 0 to 3, according to grayscale sonography, synovitis, and blood flow. Synovial lesions were evident on sonography before week 4; however, serum biomarkers slowly increased until weeks 5 and 6 (P < .05). Although both sonography and serum biomarkers correlated significantly with synovitis scoring, the correlations for the sonographically derived parameters were better. The correlation indices between pathologic scores and synovial membranes thickness, blood flow, and resistive index were 0.798, 0.557, and −0.320, respectively, whereas the correlation indices between pathologic scores and tumor necrosis factor α, interleukin 1, and C-reactive protein levels were 0.451, 0.503, and 0.529.Sonographic findings had better correlations with histologic scoring than serologic biomarkers of disease activity in the RA rabbit model, especially at early stages. Local pathologic assessment of disease status by sonography is possible.