Postprandial hyperlipidemia is associated with oxidative stress and is an important risk factor for atherosclerosisand cardiovascular disease. The aims of this study were to investigate the antihyperlipidemic effect of honey administered 5or 60 minutes before a high-fat diet (HFD), to explore the role of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA)reductase in antihyperlipidemic effect of honey and to investigate the effect of honey on postprandial oxidative stress. Ratswere fasted and randomized into 5 groups. Groups 1 and 2 were administered portable water. After 60 minutes, the groupswere given portable water and HFD, respectively. Group 3 was administered honey. After 5 minutes, the rats were givenHFD. Groups 4 and 5 were administered honey and simvastatin, respectively. After 60 minutes, the rats were given HFD.Four hours after portable water or HFD administration, the rats were sacrificed. Group 2 had significantly (p < 0.01) highertotal cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL)cholesterol, catalase activity and significantly (p < 0.05) lower high density lipoprotein (HDL) cholesterol and HMG-CoA:mevalonate (p < 0.001) compared with Group 1. Group 3 had significantly (p < 0.01) higher TG and VLDL cholesterol andlower HMG-CoA: mevalonate compared with Group 1. Groups 4 and 5 exhibited significantly (p < 0.05 or p < 0.001) higherHDL cholesterol and HMG-CoA: mevalonate and lower LDL cholesterol compared with group 2. Honey pretreatment 60minutes before HFD feeding exerts more significant antihyperlipidemic effect and attenuates more considerably postprandialhyperlipidemia-induced oxidative stress than honey administered 5 minutes before HFD in Wistar rats. This markedantihyperlipidemic effect of honey pretreatment is mediated in part via inhibition of HMG-CoA reductase.