Recently it has been postulated that membrane fatty acid composition may be involved in the pathogenesis of insulin resistance and non-insulin dependent diabetes mellitus (NIDDM). The aim of this study was to determine whether alterations in tissue phospholipid (PL) fatty acids are present in hyperglycemic and hyperinsulinemic Psammomys obesus. On a native diet of salt bush, P. obesus (Israeli sand rat) remains lean and free of diabetes; however, when placed on a normal laboratory chow, a significant proportion of these animals develops a number of metabolic disorders associated with NIDDM, providing an ideal animal model of obesity and NIDDM. Four groups of mature P. obesus were studied: group A: normoglycemic and normoinsulinemic; group B: normoglycemic and hyperinsulinemic; group C: hyperglycemic and hyperinsulinemic; and group D: hyperglycemic and hypoinsulinemic. In liver and red gastrocnemius muscle, there were no significant differences between groups A, B, and C in fatty acid composition of PL. Minor differences in individual fatty acids were demonstrated in group D animals (increased liver 20:4n-6 and increased muscle 22:5n-3); however, the unsaturation indices in liver and muscle were not significantly different between any of the groups. In considering that the minor changes in group D animals were not demonstrated in hyperinsulinemic group B animals or hyperglycemic, hyperinsulinemic group C animals, it is likely that the differences in group D animals were secondary to the more severe disturbances in glucose homeostasis and hypoinsulinemia present in these animals. The results of this study suggest that in this rodent diabetic model significant disturbances in glucose homeostasis and hyperinsulinemia may develop independently of changes in tissue fatty acid composition.