To explore the polyunsaturated fatty acids (PUFAs) on the metabolism of apoB100-containing lipoproteins in apolipoprotein E deficient (apoE^-/-) mice, which exists similar symptoms with human typeⅢ familial hyperlipoproteinemia, two months old male apoE^-/- mice were fed the perilla seed oil or safflower oil diet and the control diet, respectively, for 6 weeks. Serum lipids, apoB100 and hepatic HMG-CoA reductase were determined after 6 weeks intervention. The hepatic genes mRNA abundance involved in apoB100 containing lipoprotein metabolism were detected with real time RT-PCR. The hepatic PPARα protein expression was determined by Western blot. The hepatic lipid accumulation was detected by Oil Red O staining after frozen section. The results showed that the mice fed with the perilla seed oil diet decreased the serum LDL-C and apoB100 and HMG-CoA reductase activity. The hepatic genes such as FAS, apoB100, HMG-CoAR, ACAT2, LRP, LDLR and SREBP-1c were decreased significantly compared with the control group. The mRNA and protein expression of PPARα increased significantly in mice fed the perilla seed oil diet, while decreased significantly in mice fed the safflower oil diet compared with the control group. The mice fed the safflower oil diet increased the serum triglyceride and HDL-C and the hepatic apoB100 mRNA level compared with the control group. The hepatic lipid accumulation was decreased in the mice fed the perilla seed oil diet, and was increased in the safflower oil diet compared with the control group. The results indicated that dietary perilla seed oil decreased obviously the metabolism of apoB 100-containing lipoprotein, which was benefit for the atherosclerosis and the fatty liver diseases, providing theoretical basis for the dietary of population and the human typeⅢ familial hyperlipoproteinemia.