Objective: To observe the effect of curcumin derivatives L6H4 on rats with abnormalities of glucose and lipid metabolism, and preliminarily study the mechanism of it. Methods: Twenty-four male SD rats were randomly allocated into three groups: normal control group (NC group, n=8), high fatty group (HF group, n=8), and fatty treatment group (FT group, n=8). To fed the rats in HF group and FT group with high fat and surgar diet for 12 weeks, from the 5th week with drug treatment for 8 weeks, at the end of 12th week, the following indexes were measured respectively in each group: serum biochemical indexes, liver and skeletal muscle triglycerides, and related indicators of sugar and lipid matabolism. Observing the liver pathological changes at the same time. Results: ①Compared HF group with NC group: weight gain (P<0.05), liver weight, fasting blood glucose (FBG), fasting insulin (FINS), insulin resistance index (HOME-IR), serum triglycerides, liver triglyceride, skeletal muscle triglycerides, serum ALT, FFA, high-sensitivity c-reactive protein (hs-CRP) and interleukin 6 increased (P<0.01), adiponectin and leptin decreased (P<0.01, P<0.05, respectively). ②Compared the FT group with HF group: weight and ALT loss (P<0.01), liver weight and liver index had no obvious difference, FBG decreased (P<0.01), FINS (P>0.05), the HOME-IR decreased (P<0.01), serum triglycerides, liver triglycerides and skeletal muscle triglyceride were reduced (P<0.01, P<0.01, and P<0.05, respectively), FFA and hs-CRP reduced (P<0.01), fibroblast growth factor 21 (FGF-21) increased (P<0.01), adiponectin, interleukin 6 increased with P<0.01 and P<0.05, respectively. ③Inflammatory injury in hepatic tissue of HF groups was slight, while fatty degeneration in hepatic tissue and skeletal muscle were obvious, the condition was significantly reduced in the FT group. Conclusion: Curcumin derivatives L6H4 has the effect of controlling weight, protecting the liver function and improving the condition of insulin resistance on high fat and sugar-fed rats.