Abstract: Objective To investigate the protective effect of luteolin on nonalcoholic fatty liver disease (NAFLD) in mouse. Methods A total of 52 Kunming mice were randomly divided into control group (11 mice) and model group (41 mice). The control group was given standard diet and the model group was given high fat diet. After 8 weeks of feeding, 1 mouse in control group and 1 mouse in model group were randomly selected to confirm the model success or failure by pathological test. After model success, mice in model group were randomly divided into 4 groups, including NAFLD model group and low dose group[50 mg/(kg·d)], middle dose group[100 mg/(kg·d)]and high dose group[200mg/(kg·d)], 10 mice in each group. The mice in Luteolin group were given corresponding dose of luteolin, and the control group and the NAFLD model group were given the same amount of normal saline. After 4 weeks, the mice were sacrificed and serum triglyceride (TG), serum total cholesterol (TC), aspartate transaminase (AST) and alanine aminotransferase (ALT) levels in serum were measured, and oxide dismutase (T-SOD), glutathione (GSH) and malondialdehyde (MDA) levels, tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) levels in serum and liver tissue totals were tested. Then liver tissue sections were observed. Results Compared to control group, the TG, TC, AST and ALT levels of NAFLD model group were significantly increased, MDA, TNF-α and IL-6 levels of serum and liver tissues were significantly increased (all P < 0.05), and the T-SOD, GSH levels of serum and liver tissues were significantly decreased (all P < 0.05). Compared to NAFLD model group, the TG, TC, AST and ALT levels of low, middle and high dose luteolin groups were significantly decreased (all P < 0.05), and the MDA, TNF-α and IL-6 levels of serum and liver tissues were significantly decreased (all P < 0.05), and T-SOD and GSH levels of serum and liver tissues were significantly increased (all P < 0.05). The cells number of fatty degeneration in luteolin group was significantly improved as compared with NAFLD model group. Conclusion Luteolin can reduce the deposition of nonalcoholic fatty liver lipids, reduce the degree of oxidative stress and inflammatory reaction, and protect nonalcoholic fatty liver.