The uptake of plasma lipids into tissue was studied in normal, starved, and alloxan-diabetic rats before and after treatment with insulin, using fat emulsion and rat chylomicrons labelled with radioactive triglyceride fatty acids. — Fifteen minutes after intravenous injection of fat emulsion 97% of the label was recovered in lipid extracts of 8 different tissues; 67% was recovered after injection of chylomicrons. Most of the lipid-extractable radioactivity was found in plasma, liver, and adipose tissue, the last containing about 20% of the injected dose. In diabetic rats the lipid uptake of the liver decreased by 20±29%. This defect was not readily reversed by insulin. The uptake increased by 126±96% in the heart but returned to normal after treatment with insulin. In adipose tissue of diabetic rats the lipid uptake decreased by 80±10% or more. It was significantly stimulated 30 minutes after injecting 1 unit of insulin. The lipid uptake also decreased in adipose tissue of starved rats. In these animals it was not stimulated by insulin; however, it was stimulated with the administration of glucose. — The decrease of lipid uptake by adipose tissue was paralleled by a delayed elimination of lipid from blood plasma and vice versa. The experiments suggest that the defect of triglyceride metabolism in adipose tissue plays a major role in hyperlipaemia associated with decompensated diabetes mellitus.