Aim To observe the expression of cathepsin L(Cat L) in atherosclerotic lesion and investigate its role in lipid accumulation of macrophage. Methods Atherosclerosis model of rabbit carotid artery was established by using ringer of carotid artery.Immunohistochemisty was taken to examine the expression of Cat L in plaques.RAW264.7 macrophage was cultured and treated with various concentrations of oxidized low density lipoprotein(ox-LDL).The mRNA level,the protein expression and the activity of Cat L were detected by reverse transcription polymerase chain reaction(RT-PCR),Western blot and spectrofluorimeter,respectively.The RAW264.7 macrophage was pretreated with various concentrations of Cat L inhibitor,the accumulation of cellular lipid was detected by oil red O staining and high performance liquid chromatography(HPLC). Results Cat L was highly expressed in atherosclerotic lesion,while very weak positive staining was observed in normal vascular.After treatment with oxidized low density lipoprotein,the Cat L mRNA levels were not obviously different among groups(P>0.05).However,the protein expression and the activity of Cat L were increased with a concentration-dependent manner(P<0.05).With pretreatment of Cat L inhibitor,the deposition of lipid was inhibited responding to the inhibitor concentration. Conclusion Cat L was highly expressed in the atherosclerotic plaque and involved in the process of macrophage lipid metabolism.