Dietary supplementation of conjugated linoleic acids (CLA) is known to have some beneficial effects such as anti-carcinogenic and anti-obesity effects in several animal species, while it also induces insulin resistance and fatty liver. especially in mice. To explore the possible factors responsible for the CLA-induced insulin resistance. we examined the plasma and mRNA expression levels of several adipocytokincs. which are likely involved in the regulation of insulin sensitivity. in normal C57BL mildly obese/diabetic KK and morbidly obese/diabetic KKAy mice. Feeding a diet supplemented with 0.5% CLA oil consisting of 30.5% c9. t11-CLA and 28.9% t10. c12-CLA for 4 wk resulted in a decrease in white adipose tissue (WAT). an increase in liver weight with excess accumulation of triglyceride and insulin resistance associated with hyperglycemia and hyperinsulinemia. The plasma and WAT mRNA levels of leptin were higher in KK and KKAy mice than C57BL mice. whereas those of adiponectin were higher in C57BL mice. CLA-feeding decreased the levels of leptin, adiponectin and resistin. especially in KK and KKAy mice. In contrast, tumor necrosis factor-alpha (TNF alpha) mRNA levels were higher in KK and KKAy mice than C57BL mice. and were increased by CLA feeding. The present results thus indicate that CLA feeding promotes insulin resistance in obese/diabetic mice by at least inverse regulation of leptin and adiponectin, and TNF alpha. adipocytokines known to either ameliorate or deteriorate insulin sensitivity respectively.