Abstract: Objective To explore the expressions of sterol regulatory element binding protein 1C (SREBP-1C) and glucose-regulated protein 94（GRP-94）in hyperhomocysteinmia and evaluate the effects of endoplasmic reticulum stress proteins on hepatocytes lipids metabolize. Methods After hyperhomocysteinmia C57BL/6 mice model being induced by high methionine diet , the levels of TGE and CHO of Hepatocytes were determined, and the expressions of SREBP-1C and GRP-94 were assessed by RT-PCR and Western blot. All data were compared to control group's. Results The levels of plasmic homocysteine(Hcy) and hepatocytes TGE or CHO of high methionine diet mice at different time point were significantly ascended（P<0.05, vs 0 week）. But the plasmic TGE and CHO levels had no change.The expressions of rnRNAs and proteins of GRP-94 and SREBP-1C at different time point after mice being administrated high methionine diet were higher than that of at 0 week（P<0.05）. Conclusion It suggests that Hcy-induced endoplasmic reticulum stress causes the expression change of SREBP-1C and GRP-94, the dysregulation of the endogenous sterol response pathway .