Abstract Thyroid‐associated ophthalmopathy (TAO) is a serious, progressive, vision‐threatening and difficult‐to‐treat organ‐specific autoimmune disease. The course, therapeutic effects and prognosis of moderate to severe TAO vary greatly. High‐dose intravenous glucocorticoid (IVGC) therapy is considered a first‐line treatment for active moderate‐to‐severe TAO, but there is still insufficient evidence regarding the treatment duration. Long‐term IVGC therapy can influence the metabolism of glucose, lipids, and bone. This study was designed to compare changes in metabolic and immunological indexes as well as the magnetic resonance imaging apparent diffusion coefficient (ADC) of the extraocular muscles after 4 and 12 weeks of IVGC therapy. Forty‐eight patients with active moderate‐to‐severe TAO were included in this retrospective cohort study. Metabolism and immunological indexes were measured before and after therapy. The ADC and clinical activity score (CAS) were used to evaluate the efficacy of treatment in these patients. We found that the patients in the 12‐week group had increased fasting plasma glucose (p = 0.004), glycated hemoglobin (p = 0.028), total cholesterol (p