Aim This study examines the relationship between PPAR gamma and delta and cholesterol efflux mediated by high density lipoprotein. Methods Pooled plasma were collected from health human. Component (density 1.063 1.21 g/cm 3) was prepared by density ultracentrifugation. U937 cells were treated by cholesterol for 24 h, cell pellets were washed with PBS, then added RPMI 1640 supplemented with 1% FBS. The cells were treated by the antisense PPAR gamma and delta oligo DNA, PPAR gamma activator ciglitazone, and PPAR responsive element decoy, respectively. The effects of the oligo DNA on efflux of cholesterol was evaluated by relative radioactivity of the cell pellets. PPAR gamma and delta protein expression levels were assayed by Western blot. Results The results demonstrated that HDL promoted cellular cholesterol efflux in dose and time dependent manner reflected by radioactivity of cell pellets. It was also observed an increase in HDL mediated cholesterol efflux associated with a decrease of antisense oligo DNA of PPAR gamma, and an decrease in HDL mediated cholesterol efflux associated with decrease of antisense oligo DNA of PPAR delta, both in a dose dependent manner. PPAR activator ciglitazone stimulated the HDL mediated cholesterol efflux. Treatment with PPAR responsive element decoy inhibited the cholesterol efflux mediated by HDL. Western blot assay demonstrated that PPARgamma protein level was increased, while PPARdelta level decreased by HDL. Conclusion This study suggests that PPAR gamma may improve the cholesterol efflux mediated by HDL, PPAR delta may prevent the HDL mediated cholesterol efflux.