To examine the possible role of low-density lipoprotein (LDL) cholesterol in the enhanced norepinephrine (NE)-induced contractile response seen in spontaneously diabetic mice (db/db mice), we examined the effect of chronic administration of cholestyramine on the NE-induced contraction. Although chronic cholestyramine (300 mg/kg, po for 1 month) significantly lowered total cholesterol, high-density lipoprotein (HDL) cholesterol, LDL cholesterol, and triglyceride, the plasma glucose and insulin levels were unaffected. The enhanced NE response in diabetic mice was not affected by the chronic administration of cholestyramine. The K+-induced contractile response was not different among nondiabetic, diabetic, and diabetic mice chronically treated with cholestyramine. These results suggest that neither LDL cholesterol nor triglyceride is involved in the enhancement of the NE-induced contractile response seen in spontaneously diabetic mice.