HYPER-LIPIDEMIA is a dominant risk factor that contributes to the development and progression of atherosclerosis. Safflower is rich in the essential omega-6 and omega-3 polyunsaturated fatty acids and phenolic compounds which are known to be effective for the treatment of hyper- lipidemia. This study was performed to examine the efficacy of safflower to ameliorate the induced hyper-lipidemia in rats. The results obtained revealed that rats fed on high fat diet (HFD) significantly induced an increase in lipid profile, glucose and some liver enzymes as well as elevation of malondialdehyde (MDA) associated with a significant decrease in high density lipoprotein (HDL-C), glutathione (GSH) content and some antioxidant enzymes activity. However, when rats received HFD containing either raw or irradiated safflower (1% w/w), a significant improvement in the above mentioned parameters was seen. In conclusion, safflower supplementation in diet of rats pointed out to a promising role of safflower, a natural product, on antioxidant enzymes, liver function and lipid profile of hyper-lipidemic rats, regardless if it is irradiated or not.