The models of hyperlipidemia tilapia induced by high-fat diet were established to explore the effects of fermented mulberry leaves on serum lipid and blood glucose levels of hyperlipidemia tilapia(Oreochromis niloticus). A total of 450 male GIFT tilapia with the initial average body weight of 45 g were randomly divided into 5 groups with 3 replicates per group, and 30 fish in each replicate. The fish in normal control group were fed with a basal diet, and the other 4 groups were fed the basal diet(model control group) and diets contained 7.5% and 15.0% fermented mulberry leaves(low level fermented mulberry leaves group and high level fermented mulberry leaves group, respectively), and 0.5% ginkgo flavone(ginkgo flavone group) after the establishment of the hyperlipidemia model, respectively. The experiment lasted for 8 weeks. The results showed as follows:after feeding 5 and 8 weeks, the body weight in model control group was significantly lower than that in normal control group, low level fermented mulberry leaves group, high level fermented mulberry leaves group and ginkgo flavone group(P<0.05), but no significant difference was found between high level fermented mulberry leaves group and normal control group(P>0.05). The serum total cholesterol(TCHO) and low-density lipoprotein cholesterol(LDL-C) contents and TCHO/high-density lipoprotein cholesterol(HDL-C) in low level fermented mulberry leaves group, high level fermented mulberry leaves group and ginkgo flavone group were significantly lower than those in model control group(P<0.05), but no significant differences were found in the serum TCHO, triglyceride(TG), LDL-C contents and TCHO/HDL-C between high level fermented mulberry leaves group and normal control group(P>0.05). Compared with the model control group, the serum HDL-C content in high level fermented mulberry leaves group and ginkgo flavone group was significantly increased(P<0.05). Compared with the model control group, the serum superoxide dismutase(SOD) and catalase(CAT) activities and CAT/SOD were significantly increased(P<0.05) and the serum MDA content, hepatopancreas lipid content and hepatosomatic index(HSI) were significantly decreased(P<0.05) in normal control group, low level fermented mulberry leaves group, high level fermented mulberry leaves group and ginkgo flavone group, but no significant differences were found in above indices between high level fermented mulberry leaves group and normal control group(P>0.05). High-fat diet could significantly increase the blood glucose level in model control group, low level fermented mulberry leaves group, high level fermented mulberry leaves group and ginkgo flavone group(0 week, P<0.05); after feeding 8 weeks, the blood glucose level in high level fermented mulberry leaves group and ginkgo flavone group was significantly decreased than that in model control group(P<0.05), but had no significant difference compared with normal control group(P>0.05). These results indicate that fermented mulberry leaves can decrease the serum lipid and blood glucose levels, and enhance the antioxidant ability of hyperlipidemia tilapia with a dose-dependent manner.