This study explored the effect of water extract of mulberry leaf on lipid metabolism， to illuminate its’ lipid-lowering mechanism. Giving high-fat mice different dosage mulberry leaf water extract for 8，12 and 16 weeks， then collected their blood and livers to determine the level of blood lipid and the activity of enzymes by kits. Male mice were given high dosage mulberry leaf water extract for 12 weeks， its level of blood lipid returned to normal. Compared with HFC group， the rate of weight-gain were decreased by 22.52%， abdominal fat factors were decreased by 32.67%， contents of TC， TG， LDL-C in serum were decreased by 41.29%， 36.60% and 31.28% respectively， contents of HDL in serum were increased by 47.20%， activity of FAS in liver were decreased by 23.99%， activity of LPL， HL in liver were increased by 21.22% and 32.91%. Female mice were given high dosage mulberry leaf water extract for 8 weeks， its level of blood lipid returned to normal. Compared with HFC group，the rate of weight-gain were decreased by 26.58%， abdominal fat factors were decreased by 40.74%， contents of TC， TG， LDL-C in serum were decreased by 42.53%，41.75% and 29.33% respectively， contents of HDL in serum were increased by 22.46%， activity of FAS in liver were decreased by 22.49%， activity of HSL in liver were increased by 31.98%. Giving high-fat mice mulberry leaf water extract for a certain period， which can inhibit fat synthesis and accelerate fat decompose， to reduce fat accumulation and improve the level of blood lipid.