AIM:To investigate the effect of berberine on the morphology of orbital adipose tissue in thyroid associated ophthalmopathy(TAO). METHODS:Forty-eight patients with TAO were randomly assigned to no berberine therapy (group 1, TAO control) or berberine therapy for 4 weeks (group 2), 8 weeks (group 3), and 12 weeks (group 4) before undergoing orbital decompression. The orbital adipose tissue was obtained from the surgery, and undergone frozen section and HE staining. The morphology of adipocyte was investigated. RESULTS:The mean deviation sectional area of orbital adipocytes in normal control were 5909.4625±664.91 (pixel²), in group 1, 2, 3 and 4 were 46077.5357±11263.27, 19634.100±3512.43, 17529.69±4342.99, 27980.1304±6123.96 (pixel²) respectively. There were significantly difference in mean deviation sectional area of orbital adipocytes between normal control and TAO control, normal control and group 1. There were significantly difference in mean deviation sectional area of orbital adipocytes among TAO control and all experimental groups. The mean sectional area of orbital adipocytes in normal control were 13780.104±7542.28 (pixel²), in group 1, 2, 3 and 4 were 45210.250±25854.40, 45554.80±15544.69, 39163.94±12696.71, 27184.889±10703.85(pixel²) respectively. There were significant differences in mean sectional area of orbital adipocytes between normal control and all experimental groups, between group 1 and group 4. CONCLUSION: The mean sectional area of orbital adipocytes in patients with TAO was larger than that of normal control. The difference in sectional area of orbital adipocytes in TAO patients was larger than that of normal control. Taking berberine can decrease the difference of orbital adipocytes size in patients with TAO, and reduce the size of enlarged adipocytes to some extent.