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Background and Objectives: Different varieties of peppers have wide applications in traditional medicine. There are evidences that peppers affect some of cardiovascular diseases risk factors. The present study investigated the effect of oral red and black pepper powders on the serum levels of blood lipid profile in animal model. Materials & Methods: In this study, two groups were used as post-test with control group. Twenty one NMRI male mice were weighed and randomly divided into three groups (n=7), including a control group, fed no chili (pepper) diets, and two experimental groups, fed the red pepper and black pepper powders, each mixed with standard pellet food at a ratio of 1/15 (6/6% of the weight of food) for one month. At the end of the 30-day treatment period, the body weight of the experimental animals was determined under deep anesthesia by chloroform. Then blood samples were collected from the heart directly. Serum levels of total cholesterol, LDL-c and HDL-c were determined by colorimetric method. Results: Black pepper significantly reduced weight, total cholesterol and LDL-c, and increased the HDL-c/LDL-c ratio (p=0.003, p=0.009, p=0.001 and p=0.01, respectively). Red pepper decreased weight and total cholesterol significantly (p=0.01, and p=0.009, respectively). Conclusion: Black and red peppers in nutrition regime can cause a reduction of weight and blood cholesterol. Cholesterol lowering properties in consumption of black pepper show better than consuming red pepper in diet. Keywords: Red pepper, Black pepper, Total Cholesterol, LDL-c, HDL-c