OBJECTIVES Cow urine ark (CUA), known as "Amrita" as mentioned in Ayurveda, contains anti-hyperglycemic and antioxidant effects. Therefore, we designed the present study to evaluate the lipid lowering activity of CUA and its possible implication in metabolic syndrome. MATERIALS AND METHODS Thirty guinea pigs of either sex were divided into five groups: Group 1 and 2 serving as a vehicle and sham control, received normal and high fat diet for 60 days respectively; Group 3, 4 and 5 received high fat diet for 60 days with CUA 0.8 ml/kg, 1.6 ml/kg and rosuvastatin (1.5 mg/kg) on thelast 30 days of study period, respectively. Serum lipid profile (total cholesterol, triglycerides, LDL-C, VLDL-C, HDL-C, total Cholesterol/HDL-C) and serum enzymes (ALT, AST, ALP, LDH and CK-MB) were performed in each group at the beginning and end of the study. Histological study of liver and kidney was done in each group. RESULTS CUA (0.8 ml/kg) significantly decreased the serum triglycerides and VLDL-C, but CUA (1.6 ml/kg) decreased the total serum Cholesterol, triglycerides and VLDL-C (p < 0.05). Higher dose (1.6 ml/kg) of CUA also increased HDL-C level, significantly (p < 0.05). CUA reduced serum AST, ALP and LDH level, which was statistically significant as well, while it also decreased the accumulation of lipid in hepatocytes as compared to sham control. CONCLUSIONS CUA reduced triglycerides, increased HDL-C and found to be hepatoprotective in animals that are on a high fat diet.