Aim To investigate the effect of high cholesterol chow on high density lipoprotein (HDL) receptors in hepatic plasma membranes with 125 I-labeled HDL 3 as ligands. Methods The hepatic plasma membranes were purified by density gradient ultracentrifugation from rabbits fed with high cholesterol chow and rabbits fed with normal chow. Apolipoprotein E deficient HDL 3 was isolated from plasma of normally fed rabbits by density gradient ultracentrifugation, and labeled with 125 I by ICl method. Radioreceptor assays were carried out by incubation of the purified plasma membranes with labeled and unlabeled HDL. Results HDL receptors on hepatic plasma membranes of rabbits fed with high cholesterol chow and normal chow have an average Kd of 8.06±3.10 mg/L and 9.27±3.54 mg/L. There is no statistical difference of Kd between the two groups. But HDL receptors on hepatic plasma membranes of rabbits fed with high cholesterol chow have an higher value of Bmax than those with normal chow (2.46±0.72 mg/g vs 1.18±0.48 mg/g,P<0.001). Conclusions The high cholesterol chow can up-regulate the HDL receptors, and increase the HDL receptor activity on hepatic plasma membranes of rabbits.