Based on the finding of adipophilin expression with the cellular cholesteryl ester increasing, the aim of study was to investigate the active site of adipophilin in cellular cholesteryl metabolism. Mice peritoneal macrophages were incubated with 80 mg/L OxLDL or 80 mg/L OxLDL plus 1 mmol/L adipophilin antisense oligonucleotides respectively. At various time points, the incubated cell samples were observed with adipophilin immunofluoresence staining, flow cytometric analysis and cellular cholesterol analysis. The results shown, the antisense oligonucleotides treated cells contained significantly lower cholesteryl ester (19.9±1.9) mg/g for 72 h. It was also shown by Oil Red O staining that the experimental group cells had less lipid droplets. During 96 h, expression of adipophilin increased in both groups. At 12 h, expression of adipophilin in OxLDL incubated cells increased quicker than that of the cells in antisense treated cells. At 96 h, the level of adipophilin expression in untreated control was significantly higher than that of antisense treated cells. The amount of OxLDL taking up by the cells was also observed with Ox-r［CL-³H］LDL. During the observation, the amount of Ox-r［CL-³H］LDL taking up increased gradually in both groups, however, from 24 h the taking up amount in antisense treated cells was less than that of untreated control. There was a statistical difference between the two groups from 24 h to 96 h. The activity of ACAT in the two groups was observed as well. From 6 h to 48 h, the relative ACAT activity increased in both groups. The relative ACAT activity kept unchanged from 48 h to 96 h in the two groups. At 48 h, the relative ACAT activity in antisense group was significantly lower than that of control group. The activity of ACAT was related to adipophilin expression but was not a linear relationship. This meant, at least partly, expression of adipophilin was related to cellular taking up of lipoproteins and to ACAT activity. Therefore, it is indicated that adipophilin has a role in metabolism of cellular lipid droplets and adipophilin is associated with ACAT.