The present study addresses the insulin sensitivity in mice deficient in LXRbeta (LXRbeta(-/-)) as well as in wild type (wt) mice assessed by hyperinsulinemic euglycemic clamp. Wt and LXRbeta(-/-) mice were fed either a normal chow diet or a high fat and high cholesterol diet (HFCD), and insulin sensitivity was assessed by hyperinsulinemic euglycemic clamps. We show that LXRbeta(-/-) mice have reduced insulin clearance during hyperinsulinemic clamps upon feeding both HFCD and a regular chow diet. Moreover we also observed reduced hepatic inflammation in LXRbeta(-/-) mice compared to wt mice upon feeding an HFCD, despite equal levels of hepatic steatosis. In summary, our results indicate that LXRbeta(-/-) mice have reduced insulin clearance during hyperinsulinemic euglycemic clamps and also reduced hepatic inflammation upon feeding an HFCD for 26weeks.