Aim To investigate the effect and mechanism of heparan sulfate proteoglycan and heparin on accumulation of lipid in macrophages.Methods Lipid accumulation in macrophages was observed with Sudan Ⅳ stain. Cholesterol content in macrophages was detected with enzyme fluorescence assay. The activity of scavenger receptor of macrophage was assessed by examing the degradation rate of 125 1 labeled oxidized low density lipoprotein (OLDL).Results More red particles stained with Sudan Ⅳ were seen in macrophages incubated with OLDL (100 mg/L). The red particles in macrophages incubated with OLDL (100 mg/L) plus heparan sulfate proteoglycan (HSPG, 15. 5 mg/L) or with OLDL (100 mg/L) plus heparin (HP, 200 mg/L) were far less than that with OLDL only. The total cholesterol and cholesteryl ester in macrophages incubated with OLDL plus HSPG or with OLDL plus HP were significantly lower than that with OLDL (P〈0.05: P〈0.01).The degradation rate of 125 I labeled OLDL of macrophages incubated with HSPG or with HP were lower than control.Conclusion HSPG and HP may inhibit lipid accumulation in macrophage and formation of foam cell possibly through down-regulating the activity of scavenger receptor of macrophage and decreasing the intake of OLDL.