AimTo investigate the effect and mechanism of prostaglandin E1 on atherosclerotic vulnerable plaque in rabbits.Methods22 rabbits were fed a 1% cholesterol diet 2 weeks prior to and 7 weeks after balloon injury of the abdominal aorta. Thereafter the atherogenic diet was replaced with a regular diet, and rabbits were randomly divided into 3 groups for 4 weeks treatment: control group, prostaglandin E1 group and simvastatin group. At the end of week 13, all rabbits were challenged with injection of Chinese Russells viper venom and histamine. Serum, plaque morphology, plaue composition and inflamatory expression studies were performed.ResultsProstaglandin E1 did not alter serum lipid levels. Prostaglandin E1 significantly increased the thickness of the fibrous caps (101.72±34.89 μm vs 79.86±16.98 μm, p<0.01) and decreased plaque vulnerability index (0.94±0.27 vs 3.83±1.45, p<0.01); Prostaglandin E1 attenuated macrophage accumulation (p<0.01) and MMP-1, MMP-9 expression (both p<0.01) within the plaque, and there was no statistical difference between prostaglandin E1 group and simvastatin group.ConclusionProstaglandin E1 effectively enhanced stability of vulnerable plaque in rabbit model independent of serum lipid levels, in which inhibiting macrophage accumulation and inflammatory expression within plaque may play an important role.