AIM:: To quantify the progression and severity of mouse collagen-induced arthritis (CIA) using an in vivo imaging tool, F-fluorodeoxyglucose (F-FDG) PET/CT and validate it against gold standard ‘histopathological’ evaluation. METHOD:: The PET radiotracer F-FDG, a marker for glucose metabolism, was injected in mice at different stages of CIA and the radiotracer distribution was imaged using a PET scanner. A sequential CT scan provided correlated anatomy. Radiotracer concentration was derived from PET/CT images for individual limb joints and on a per-limb basis at different stages of the disease. The imaging outcomes were subjected to correlation analysis with concurrently measured clinical and histological score. RESULTS:: Clinical and histological score, and hence disease severity, showed a strong linear correlation (r = 0.71, P = 0.001 and r = 0.87, P < 0.001, respectively) with radiotracer concentration measured from PET/CT during the progression of CIA. CONCLUSIONS:: The strong positive correlation of the F-FDG PET/CT findings with the histopathological evaluation at different stages of the disease suggest the potential of this imaging tool for the non-invasive assessment of progression and severity in mouse autoimmune arthritis. Thus, in preclinical studies, F-FDG PET/CT can be considered as a non-invasive tool to develop novel therapies of inflammatory arthritis.