The apoptosis and the expression of tumor suppressor gene p53 in hypercholesterolemia (HC)-induced renal injury were investigated in rats. A high cholesterol diet (HCD)-induced HC rat model was made and serum lipid, urinary protein excretion (UPE) and N-aceto-β-D-glucosidase (NAG) were measured. The levels of malondialdehyde (MDA), as an index of lipid peroxidation, in renal cortex and serum were compared between the two diet groups. Apoptosis and p53 expression were determined by TUNEL and immunohistochemistry, respectively. In the HCD-induced HC group, serum total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) as well astriglyceride (TG) were significantly increased, while the level of high density lipoprotein-cholesterol (HDL-C) decreased. Meanwhile, increased excretions of UPE and NAG in urine were observed, which were accompanied with a decrease in urinary creatinine clearance (Ccr) and indicated both glomerular and tubular damages. In addition, apoptotic cell death coexisted in the kidney, as revealed by increased TUNEL positive cells. Finally, an increase in p53 expression was observed in tubuli, but not in glomeruli. Both TUNEL positive cells and p53 expression were found to be correlated to the level of renal cortical MDA (r=0.817, P