Objective To investigate the effect of Glycyrrhizin combined with puerarin on serum Leptin and insulin resistance in non-alcoholic fatty liver disease(NAFLD) patients.Methods One hundred and twenty patients with NAFLD were randomized into 4 groups,which were control group,compound Glycyrrhizin group,puerarin group,combined group,and each group was 30 cases.Patients in control group were received the regular liver protecting therapy including vitamins,amino acids,glucurolactone,in compound Glycyrrhizin group were given 60 ml compound glycyrrhizin solution (iv),in puerarin group were given puerarin at dose of 400 mg by intravenous infusion,and in combined group were given both compound glycyrrhizin and puerarin combination.All treatment period was 4 weeks.The levels of serum serum alanine aminotransferase (ALT),aspartate aminotransferase (AST),total cholesterol (TC),triglyceride (TG),leptin (LP),fasting blood glucose (FBG) and insulin(INS) were measured,and the insulin resistance index(IRI) was calculated.The liver CT image of patients were performed by Germany Siemens dual source CT instrument.Results The levels of serum ALT,AST,TC,TG,LP and IRI in control group at before and after treatment were ((83.08 ± 115.68) U/L vs.(43.32 ±11.72) U/L,(52.12±15.62) U/Lvs.(36.08 ±7.28) U/L,(6.20±1.30) mmol/Lvs.(5.60 ±0.70) mmol/L,(2.70 ±0.50) mmol/L vs.(2.10 ±0.40) mmol/L,(14.63 ±3.26) μg/L vs.(7.61 ± 2.46) μg/L,(7.9 ± 1.8) vs.(7.0 ± 1.2)),and the difference were statistically significant (t =12.828,4.244,16.648,21.442,3.341,16.152 respectively,P ＜ 0.01).The levels of serum ALT,AST,TC,TG,LP and IRI in compound glycyrrhizin group after treatment were ((43.28 ± 11.06) U/L,(37.28 ± 7.22) U/L,(5.70± 0.80) mmol/L,(2.20 ± 0.50) mmol/L,(7.89 ± 2.26) μg/L,(7.1 ± 1.6) respectively,significant different from before treatment ((83.06 ± 14.38) U/L,(51.68 ± 15.48) U/L,(6.30 ± 1.50) mmol/L,(2.60 ± 0.40) mmol/L,(15.13 ± 3.87) μg/L,(7.8 ± 2.2) respectively,t =8.893,4.225,16.520,24.708,6.353,21.137 respectively,P ＜ 0.01).The levels of serum ALT,AST,TC,TG,LP and ISI in puerarin group after treatment were (44.26 ± 9.68) U/L,(36.86 ± 6.88) U/L,(5.60 ± 0.70) mmol/L,(2.26 ± 0.48) mmol/L,(6.89 ± 2.18) μg/L,(7.0 ± 1.8) respectively,significant different from that before treatment ((82.68±14.36) U/L,(50.06±15.23) U/L,(6.20±1.60) mmol/L,(2.70±0.52) mmol/L,(15.68 ±3.26)μg/L,(7.7 ±2.8) respectively,t =7.087,8.138,18.159,7.244,7.470,32.283 respectively,P ＜ 0.01).The levels of serum ALT,AST,TC,TG,LP and ISI in combined treatment group after treatment were (22.28 ± 9.38)U/L,(28.48 ± 9.06) U/L,(5.00 ± 0.60) mmol/L,(1.70 ± 0.40) mmol/L,(4.63 ± 2.36) μg/L,(6.20± 1.6) respectively,significantly different from that before treatment ((84.62 ± 14.88) U/L,(49.12 ± 16.56)U/L,(5.70 ± 1.60) mmol/L,(2.78 ± 0.50) mmol/L,(14.78 ± 3.68) μg/L,(7.6 ± 2.1),t =14.255,11.272,8.371,9.941,8.102,37.626,P ＜ 0.01).The levels of serum ALT,AST,TC,TG,LP and ISI of patient were no significant difference before treatment,but after treatment,these indexes in combined therapy group were the lowest among 4 groups (P ＜ 0.05).And there were no significant difference among control group,compound glycyrrhizin group,puerarin group (P ＞ 0.05).Conclusion Compound glycyrrhizin combined with puerarin is proved to be an effect treatment method for NAFLD through decreasing serum leptin,improving insulin resistance.