Normal blood lipids concentration has a key role in reducing of cardiovascular mortality .The present study is aimed to examine the extract of rhubarb on lipid profile and histological changes of liver in rats received high cholesterol diets. Extraction of fresh leaves of rhubarb was carried by maceration process and ethanol 70% was applied as a solvent and. The crude extract was collected was for study. Doses of 500, 666 and 1000 mg/kg BW was used in animal study. Sixty Wistar male adult rats (180-250 gram) divided in 5 groups. The first group (negative control group) received and distilled water. The second group received high fat diet (%2 cholesterol and 2.5% acid colic) for 8 weeks. The prevention group 1, 2 and 3 received high fat diet and leaf extract at doses of 500, 666 and 1000 mg per kg body weight respectively orally for 8 weeks. In the last day all animals have anesthetized, serum samples were prepared for biochemical tests and tissue samples taken from livers for histology studies. Data analyzed using One-way ANOVA and P<0.05 was recognized significant. No significant difference was seen in triglyceride, LDL cholesterol, blood urea nitrogen, ureic acid, glucose, alanine transferase, asparat transferase and alkaline phosphatase in treatment group compare to control group. However, the serum concentration of total cholesterol has significant difference in prevention 2 and 3 compared with the positive control group. A decrease in serum levels of MDA and increase in antioxidant activity have shown in the prevention groups compared with the negative control. Furthermore, histological examinations of liver showed the fatty liver in positive control group; however liver histology in treatment groups at maximum dose was normal compare to positive control. The extract of rhubarb at doses of 666 and 1000mg/kg BW decreases the total cholesterol in rats fed high cholesterol diet and no effect on other biochemical parameters. A significant increase in antioxidant activity was reported in treatments groups.