Objective To investigate the thyroid ultrastructural pathological changes of diabetes mellitus (DM) rats as well as the intervention effects of insulin and aminoguanidine. Methods Totally 87 rats were treated with streptozotocin to establish DM animal models and divided into DM group（EM>n/EM>=27）,insulin intervention group(EM>n/EM>=32) and aminoguanidine intervention group(EM>n/EM>=28),25 rats were taken as normal controls. Twelve and 20 weeks after the animal model establishment, animals were sacrificed, thyroid tissue was taken and ultrastructure was observed. Results In the thyroid of DM rats, follicular epithelial cells present as applanate shape, microvilli were depleted, rough endoplasmic reticulum dilated to irregular vesicular. None pinocytotic vacuole and casual primary or secondary lysosome were seen. Follicular cavity was dilated, colloid in the cavity had higher electronic-density. Interstitial edema, capillary base lamian was thickened at different stage. Proteo-substance deposition with granulo-shape, cloud shape or homogeneity appeared. The number of thyroid parafollicular cells increased. But endocrine granule in parafollicular cells was few. When compared with DM group, the thyroid tissue injury of insulin intervention group and aminoguanidine intervention group were lessened to different degree. Conclusion The hypofunctional thyroid follicular cells, large quantity of proteo-substance deposition in the interstitium and increased parafollicular cells of DM rats may be related with hyperglycemia toxicity. Insulin and aminoguanidine treatment have some protection effects.