Curcumin has been shown to have beneficial effects on pathogenic factors involved in the development of atherosclerosis. The aim of this study was to assess the effects of curcumin phytosomes on atherosclerosis induced by high-fat diet in rabbits. A total of 16 adult male New Zealand white rabbits (1.8-2 kg) were fed with a diet containing 0.5% cholesterol for 4 weeks. The rabbits were randomly divided into four groups of four animals each. Group I orally received PBS for 4 weeks. Group II animals were treated with curcumin-phosphatidylcholine solid state dispersion (Meriva®, Indena, Italy) suspended in normal saline at doses equivalent to 100 mg/kg of curcuminoids per day p.o., for 4 weeks. Groups III and IV were treated with curcumin-phosphatidylserine solid state dispersion (Meriserin®, Indena, Italy) suspended in normal saline at doses equivalent to 10 and 100 mg/kg of curcuminoids, respectively, per day p.o., for 4 weeks. For atherosclerosis evaluation, histological examinations on aortic arch section were performed. Blood samples were obtained to determine lipid profile and high-sensitivity C-reactive protein (hs-CRP) levels. Curcumin-phosphatidylserine (100 mg/kg) therapy resulted in a significant reduction in grading of atherosclerotic plaque and intima/media thickness ratio (P