Background: Tree peony (Paeonia ostii) seed oil is rich in different unsaturated fatty acids, including monounsaturated fatty acids (MUFA), n-3 and n-6 polyunsaturated fatty acids (PUFA). Health benefits of this edible plant oil as a whole are barely known yet. In this study, we experimentally investigated benefits of dietary tree peony seed oil (PSO) in dyslipidemia-associated metabolic diseases using a high fat diet hamster model.Methods: High fat diets (HFD) containing 15 % coconut oil (CO) or PSO were first developed based on the rodent chow diet. Fatty acid profiles of diets and red blood cells (RBC) from animals fed these diets for 8 weeks were analyzed and compared. Effects of these oil supplements on triglycerides and cholesterol levels were characterized. Benefits on fatty liver progress were also investigated in this animal model. Results: HFD fortified with 15% PSO was abundant in different unsaturated fatty acids, containing 40% α-linolenic acid, 27% linoleic acid and 23% oleic acid, respectively. Compared to the control group with 15% CO, animals with 15% PSO displayed dramatic alteration of in vivo fatty acid profile in RBC, featured with a significant increase in n-3 but no change in n-6 PUFA, resulting in decreased ratio of n-6 to n-3 PUFA. PSO intervention also remarkably reduced triglyceride levels in both blood and adipose tissues, while did not affect circulating cholesterol. Moreover, benefits on liver health were observed in the PSO group, evidenced with reduced hepatic steatosis and improved hepatic histology. Conclusion: These data altogether demonstrated multifaceted benefits of dietary PSO in reducing important risk factors of dyslipidemia-associated cardiovascular and liver diseases.Keywords: Peony seed oil, High fat diet, Triglyceride, Cholesterol, Hepatic steatosis