Seven- week- old male Sprague- Dawley ( SD) rats were divided into six groups ( LFC, LFD, HFC, HFD30, HFD40, HFD50) to determine whether animals receiving a low- fat ( LF) diet plus nicotinamide- streptozotocin ( NA- STZ) injection or animals receiving a high- fat ( HF) diet plus STZ injection provide a better model of type 2 diabetes. After 2 weeks of feeding, diabetes was induced by intraperitoneal injection of NA ( 230 mg/ kg BW) and STZ ( 65 mg/ kg BW) in LFD, and STZ 30, 40, 50 mg/ kg BW to HFD30, HFD40, HFD50 groups, respectively. Fasting blood glucose at 48 - 72 h and nonfasting blood glucose at 1 week after STZ injection were 1200 and 1600 mg/ dl, respectively, in HFD40 and HFD50 groups while no significant difference was observed among other groups. Serum insulin concentration was significantly ( p < 0.05) decreased in LFD, HFC, HFD30, and HFD40 groups compared to LFC and HFD50 groups. One animal died and other animals of the HFD50 group were in a critical condition. Serum lipid and liver glycogen were increased in HFD groups compared to other groups. The results of this study suggest that the HF diet-fed, 40- mg/ kg BW STZ- injected SD rat is better than the LF diet- fed NA- STZ- injected rat as an animal model of human type 2 diabetes. Copyright (c) 2007 S. Karger AG, Basel.