Abstract: ObjectiveTo determine the mediating role of hypothalamic-pituitary-adrenal axis (HPA) and hypothalamic-pituitary-thyroid axis (HPT) axis in anxiety disorder in patients with diabetes mellitus. MethodsA total of 562 hospitalized patients with anxiety disorder participate in the study. Serum thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), free triiodothyronine (FT3), total tetraiodothyronine (TT4), free tetraiodothyronine (FT4）, adrenocorticotropic hormone (ACTH) and cortisol (PTC) were measured. Glucose tolerance test (OGTT) was performed, estimating insulin resistance index (HOMA IR) and insulin sensitivity index (WBISI). ResultsOf the participants, 83 (14.8%) had diabetes. In those who were younger than 40 yr., the diabetic patients were more likely to have abnormal FT4 and HPT ( P<0.05). The patients with diabetes were more likely to be older (OR=1.067，95%CI：1.041-1.094， P=0.000） and have higher FT4 （OR=1.104，95%CI：1.022-1.193， P=0.012） and PTC （OR=1.001，95%CI：1.000-1.003， P=0.025）. Insulin resistance index increased while insulin sensitivity index decreased （ P<0.05） with abnormal PTC and HPA axis. Insulin sensitivity index decreased ( P<0.05) when ACTH, HPT axis, FT4 and TT3 were abnormal. ConclusionAbnormal HPA or HPT axis mediates diabetic complications in patients with anxiety disorder. Early interventions on neuroendocrine hormone abnormality may help prevent diabetes in patients with anxiety disorder.