Aim of the study: Chinese prescription Kangen-karyu is clinically used as a treatment for cardiovascular diseases, and we have reported the beneficial effects on chemically induced hyperlipidemic animal models. The present study was investigated to evaluate the hypolipidemic effect of Kangen-karyu in type 2 diabetic db/db mice which has not been explored yet. Materials and methods: Male db/db mice were divided into three groups, vehicle (control), Kangen-karyu 100, or 200 mg/kg body weight/day, and orally administered for 5 weeks every day. Age-matched nondiabetic m/m mice were used as a normal group. Results: Serum triglyceride (TG) and total cholesterol levels in db/db mice were increased compared with those of m/m mice. However, the administration of Kangen-karyu reduced hyperlipidemia in db/db mice through a decline in the serum levels of TG and total cholesterol. The hepatic TG and total cholesterol levels of db/db mice were markedly higher than those of m/m mice, but these elevated lipid levels were significantly reduced by 200 mg/kg Kangen-karyu administration. Also, oil red 0 staining showed that the increased lipid deposition level in the liver of db/db control mice was improved by Kangen-karyu administration. The expression of sterol regulatory element-binding protein-1 in the liver of db/db mice was significantly down-regulated by the administration of Kangen-karyu at a dose of 200 mg/kg body weight. Kangen-karyu caused a slight elevation in the expression of peroxisome proliferator-activated receptor a in the liver of db/db mice. Conclusions: This study provides scientific evidence that Kangen-karyu improves hyperlipidemia and lipid deposition via the regulation of hepatic SREBP-1 expression in type 2 diabetic db/db mice. (C) 2010 Elsevier Ireland Ltd. All rights reserved.