The purpose of the present experiment was to investigate if the modulation by insulin of liver microsomal desaturase activities in the spontaneously diabetic adult male Bio-Breeding (BB) rat, with destructive insulitis resembling the lesions described in the human Type I (insulin-dependent) diabetes, corresponds to modifications in fatty acid composition, reflect of changes in fatty acid desaturation. We observed no significant differences between BB rats, during the hyper-(48 h), the normo-(17 h) and the hypo-glycemic (3 h) periods which followed the insulin injection, and control rats for the fatty acid composition of liver total lipids, phosphatidylethanolamines, phosphatidylcholines, triacylglycerols, cholesterol esters and non esterified fatty acids. On the other hand, linoleic acid of BB rats liver phospholipids increased, comparatively to control rats, while arachidonic acid decreased, in agreement with previously reported results on chemical diabetes and consistent with a defective delta 6 desaturation, particularly during the normo-and hyper-glycemic periods, and the fact that control of membrane lipid composition is multifactorial.