Objective   To explore the effects of the high methionine intake on lipids metabolism of liver and the possible mechanisms. Methods  Twenty healthy 6-week old SD rats were selected and randomly divided into the control group and methionine group. After 2 weeks of acclimation, rats of the control group were fed with standard chow and received PBS gavages, while rats of the methionine group were fed with standard chow and received methionine gavages for 8 weeks. The body weight of rats was measured every week. The samples of blood and liver tissue were collected, the weight of livers was measured, and the organ coefficient was calculated after rats were sacrificed. The liver tissue was sliced and H-E stained and the morphologic observation was performed. Biochemical indexes of serum were detected by automatic biochemical analyzing system. The level of serum homocysteine was detected by ELISA. The gene expression levels of enzymes relevant to lipid metabolism were detected by quantitative real-time PCR. HepG2 cells were cultured in vitro and stained by oil red O. The effects of methionine load or homocysteine treatment on the lipids deposition in HepG2 cell were observed under optical microscope. The change of expression level of n-SREBP1c was detected by Western blotting after being treated by homocysteine. Results The difference of increase of body weight between the control group and methionine group was insignificant, while the organ coefficient of methionine group was significantly higher than that of the control group (P<0.05). Rats of the methionine group developed mild microvesicular steatosis, but no inflammation or obvious hepatic dysfunction was found. Levels of plasma homocysteine, TC, and HDL of the methionine group were significantly higher than those of the control group (P<0.05). The differences of mRNA expressions of Fas, Acc, Scd1, and Cpt1α in the liver tissue between two groups were not statistically significant (P>0.05). Treatment with methionine or homocysteine led to obvious lipids deposition in HepG2 cells. The expression of n-SREBP1c in HepG2 cells significantly increased after being treated by homocysteine. Conclusion   Excessive methionine intake may result in mild hepatic steatosis, which is associated with the increase of homocysteine in blood. Moderate increase of homocysteine level caused by methionine load can effect the lipids metabolism of liver by regulating the activity of a key transcription factor of lipids metabolism of hepatic cells.