The herb Acanthopanax senticosus was cultured from a cell suspension by a proprietary process, and evaluated for protective effects against obesity in C57BL/6J mice fed high fat diets. Forty 4-week-old male C57BL/6J mice (n = 10) were fed either a normal diet (10 kcal fat%) or high fat diet (60 kcal fat%) given with or without oral administration of A. senticosus extract (ASE; 0.5 g/kg of body weight) for 12 weeks. Feed consumption was not different among the groups, but energy intake was higher in the groups fed high fat diets than in the groups fed normal diets. Body weight gain, abdominal fat accumulation, and serum leptin concentrations were significantly higher in the high fat-fed groups than the other groups. Animals fed the high fat diet had significantly higher low-density lipoprotein (LDL)-cholesterol in serum and higher triglyceride accumulation in liver, but the ASE supplement restored both to the same levels as in the animals fed low fat diets. Total carnitine concentration were not significantly different between the two diet groups; also the oral administration of ASE did not alter carnitine status. Accordingly, the current results suggest the oral administration of ASE seemed to lower the weight gain, serum LDL-cholesterol concentration, and liver triglycerides accumulation in mice with obesity induced by high fat diets. These results seemed to suggest that supplementation with ASE might have a role in the prevention of obesity in high fat-fed mice.