The objective of this study was to determine the effects of a Scutellaria baicalensis water extract (SDWE) on lipid levels, lipid peroxidation and antioxidant enzyme activities on rats fed a high fat diet for 6 weeks. Thirty-two male Sprague-Dawley rats (4-weeks-old) were randomly divided into four groups: normal diet and deionized water (ND), normal diet and Scutellaria baicalensis water extract (NDS), high fat diet and deionized water (HFD), high fat diet and Scutellaria baicalensis water extract (HFDS). The food intakes were significantly lower, but the food efficiency ratios were significantly higher in the high fat diet groups than those in other groups. The level of HDL-cholesterol and HDL-cholesterol/total cholesterol ratio in plasma were significantly higher and AI (atherogenic index) in HFDS group was significantly lower than that in HFD group. The level of triglyceride in plasma was significantly decreased in SDWE groups. The triglyceride of liver was significantly increased in the high fat diet groups and the total cholesterol of liver in the HFDS group was significantly lower than that in the HFD group. The plasma and liver concentrations of thiobarbituric acid reactive substances (TBARS) in the NDS group were significantly lower than those in the ND group. The total antioxidant status (TAS) in plasma was significantly increased in the HFDS group compared to the HFD group. The activities of SOD, catalase and GST were significantly increased in SDWE groups compared to ionized water groups. The activity of GSH-Px and the concentration of GSH in liver in the HFDS group were significantly higher than those in the HFD group. These results suggest that a supplement of SDWE on rats fed high fat diet reduce levels of lipid and lipid peroxidation in plasma and liver and improve the antioxidant defense systems.