AbstractGonadal and perirenal fat pads from markedly obese mice show pathological changes associated with the appearance of many large macrophages, small mononuclear cells resembling lymphocytes, and polymorphonuclear cells. The first recognizable changes are always associated with necrosis of the fat cell membrane. Advanced stages also show reduction of the number of fat cells, formation of large fat vacuoles and cysts, and predominance of innumerable pathological cells. The extent of tissue changes varies considerably even within one fat pad but is dependent on the degree and duration of obesity. Animals weighing less than 45 gm are only occasionally, heavier mice almost regularly, affected. The nitrogen content of normally healthy adipose tissue decreases as the animals grow older and fatter, while fat pads exhibiting tissue pathology show the expected increase in the protein and water content, and a reduction of the lipid content. The pathological changes were observed in obese‐hyperglycemic mice, in several strains of mice made obese by the administration of goldthioglucose, and in four old and very fat controls. These four controls were the only ones in several hundred normal mice examined which showed changes. Few and only minor pathological changes were noted in subcutaneous fatty tissue of mice which showed marked pathology of the abdominal fat pads.