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The effects of resveratrol on various conditions have been widely studied previously. This paper aimed to investigate the influence of resveratrol on atherosclerosis (AS). Twenty-four New Zealand male rabbits were randomly and equally assigned to the normal diet group (NDG), fat diet group (FDG), and fat diet with resveratrol group (80 mg/kg/d, RFG). Biochemical indicators from blood samples were analyzed at baseline and 3 months to investigate the effects of resveratrol on blood lipid, lipoprotein-associated phospholipase A2 (Lp-PLA2), liver, and renal function. The indicators including alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CREA), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and Lp-PLA2. At 3 months, arteries were stained with hematoxylin and eosin to study the influence of resveratrol on the aortic intima, smooth muscle layer, and the intima/media ratio. Comparisons of weight, ALT, AST, CREA, TG, TC, HDL-C, LDL-C, and Lp-PLA2 among the three groups showed no significant difference at baseline. However, at the end of 3 months, significant differences were observed in AST, CREA, TC, HDL-C, LDL-C, and Lp-PLA2 between the three groups (P < 0.05). In pairwise comparison, CREA, TC, LDL-C, and Lp-PLA2 had significant differences between any two groups (P < 0.05). In addition, there were significant differences in the AST and HDL-C levels between RFG and NDG groups (P < 0.05). Meanwhile, the HDL-C levels were also significantly different between the FDG and NDG groups (P < 0.01). The histologic analysis also showed that the thickness of the aortic intima and the ratio of the intima and aortic tunica media (P < 0.05) significantly decreased in RFG compared to FDG. Resveratrol may have an antiatherosclerosis effect on a rabbit model of AS. [ABSTRACT FROM AUTHOR]