Abstract: Objective:To investigate the effect of melatonin(MT) on the development of nonalcoholic fatty liver disease(NAFLD) in rats with high fat diet and observe the changes of free fatty acid (FFA),to evaluate the protective mechanism of MT on NAFLD.Methods:Fifty male Wistar rats were randomly divided into five groups:control group,model group and the different groups with melatonin at low does,moderate does and high does(MT1,MT2 and MT3 groups).The rats in MT1,MT2 and MT3 groups and model group were fed with high fat diet for 12 weeks while with common diet in normal control group.MT was injected intraperitoneally at 2.5 mgkg-1d-1,5.0 mgkg-1d-1 and 10.0 mgkg-1d-1 respectively in MT1,MT2 and MT3 groups.All rats were sacrificed after 12 weeks.Histopathological changes in liver were observed.The levels of serum alanine aminotransferase (ALT),aspartate aminotransferase(AST),serum and hepatic triglyceride(TG),total cholesterol(TC) and FFA were measured.Results:High fat diet for 12 weeks established rat NAFLD model successfully.Compared with model group,hepatic steatosis was improved in melatonin-treated groups.Serum AST level in model group was higher than in control group(P 0.05),while serum TG level was lower than in control group(P 0.05).The levels of hepatic TC and TG were significantly higher than in control group(P 0.01).Serum ALT level in MT1 group was higher than in control group(P 0.05) and serum TG level in MT1 and MT2 groups were less than in control group (P 0.05).The hepatic TC level in MT1 group,the levels of hepatic TG in MT1,MT2 and MT3 groups were higher than in control group (P 0.01).The level of hepatic TC in MT3 group was lower than in model group (P 0.01).The serum FFA level in model group was higher than in control group(P 0.05 to P 0.01).Compared with model group,serum FFA level in MT groups were reduced(P 0.05 to P 0.01).The hepatic FFA level in model group was higher than in control group(P 0.01).The hepatic FFA content in MT2,MT3 groups were lower than in model group(P 0.01).Conclusions:Melatonin plays the protective and therapeutic effect for NAFLD in a dose dependent manner,may be related to decreasing the production of FFA which improving oxidative stress and depressing lipid peroxidation in rat with high fat diet.