We studied the effects of 2 different dosages of highmolecular- weight poly-γ-glutamic acid (hm γ-PGA) derived from Bacillus subtilis chungkookjang on lipid metabolism in a high-fructose diet-induced hypertriglyceridemic animal model. For 4 weeks, rats were fed either AIN-93 diet (normal control, NC; n = 10) or modified AIN-93 diet in which cornstarch was substituted with 63% fructose (n = 30) to induce hypertriglyceridemia. After 4 weeks, the hypertriglyceridemic rats were treated with daily oral doses of 0 mg (hypertriglyceridemic control, HC), 2.5 mg (hypertriglyceridemic, low hm γ-PGA, HL), or 5 mg?kg?bw-1?d-1 (hypertriglyceridemic, high hm γ-PGA, HH) hm γ-PGA for 4 weeks. The HL and HH groups exhibited significantly lower levels of serum triglyceride, total cholesterol, LDL cholesterol, and free fatty acids than the HC group. The administration of hm γ-PGA reduced serum ALT and AST levels. The activities of lipogenic enzymes such as hepatic malic enzyme and glucose-6-phosphate dehydrogenase as well as glucose-6-phosphate dehydrogenase mRNA expression were significantly decreased by hm γ-PGA administration (p < 0.05). These results indicate that hm γ- PGA has an anti-hypertriglyceridemic effect in highfructose diet-induced hypertriglyceridemic rats.