The purpose of this study was to examine the long-term effects of synthetic diet on the sand rat Harderian gland. From the third month, animals showed a diabetic syndrome characterized histologically by Harderian gland necrotic changes. Some gland tubules and melanocytes were disintegrated and numerous mast cells were densely populated in the connective capsule of the gland. Moreover, luminal porphyrin accretions and cellular debris were often associated with alcian blue positive materials. If the synthetic diet lasted more than 6 months, the gland was strongly damaged and numerous plasma cells, macrophages, and lymphocytes infiltrated the gland. These results clearly demonstrate that the sand rat Harderian gland is affected by the diabetic syndrome induced by the synthetic diet.