Several methods, including PepTag® Assay, RT-PCR, Western blot, oil red staining and HPLC, were used to explore the role of PKC in lipid-accumulation mediated by adipophilin in THP-1 macrophage treated with PKC activator PMA and inhibitor Calphostin C. 100 nmol/L PMA activated cytomembrane PKC activity ((0.2514±0.0154) U/ml), also synergistically enhanced the expressions of PKCα, PPARγand adipophilin and the lipid-accumulation in the presence of oxLDL. Together with oxLDL, PMA stimulated the ratio of intracellular CE/TC to (69.8±9.5) %. 300 nmol/L Calphostin C inhibited cytomembrane PKC activity((0.0927±0.0056) U/ml) of lipid-loaded THP-1 macrophage, reduced intracellular lipid droplets and the ratio of intracellular CE/TC ((40.1±9.1) %). Calphostin C downregulated the PKC activity and the expressions of PKCα, PPARγ and adipophilin in a dose-dependent manner. 400 nmol/L Calphostin C ultimately reverse the effect induced by 50 mg/L oxLDL. In conclusion, the changes of PKC activity can have effects on the lipid-accumulation mediated by adipophilin, PPARγ may play an important role in the regulation mechanism.