Abstract: Objective: To observe the change of eIF-2a PERK/ and IRE-1/XBP-1 pathway inducedby endoplasmic reticulum stress in nonalcoholic fatty liver disease and explore the role of exercise and dietary modification and its mechanism. Methods: 12 rats were randomly selected from 42 rats as the control group, the rest 30 rats were the model group. Control group was fed withordinary diet, model group was fed with high-fat diet. At the 8th week of experiment, 6 rats in control and model group were respectively chose for liver pathological to determine whether NAFLD model was successfully made. Model group were randomly divided into 4 groups: model group (M), exercise group (EM), diet modification group (FM) and exercise combined with diet modification group (EFM), each 6 rats. The remaining 6 rats of control group were as C group . Group C was continued to ordinary diet. Group M and EM were continued to high fat diet. Group FM and EFM were fed from high fat diet to ordinary diet. Group EM and EFM were intervened by aerobic swimming exercise for 8 weeks until the end of experiment. We observed the pathological changes in liver tissue by HE staining. Western blot was employed to explore the protein expression of eukaryotic initiation factor 2 α(eIF-2a) and protein kinase R-like endoplasmic reticulum kinase (PERK) and inositol-requiring Enzyme 1(IRE-1) and X-box-binding Protein 1( XBP-1 ). Results: (1) Compared to group C, hepatocyte steatosis is aggravating and protein expression of PERK/eIF-2a and IRE-1/XBP-1 pathway gene increased in M group; (2) Compared to group M, liver steatosis relived and protein expression of PERK/eIF-2a and IRE-1/XBP-1 pathway gene reduced in intervention groups; (3)The result of two-way anova in Group M and EM and FM and EFM showed that exercise and diet had a main effect on protein expression of PERK/eIF-2a and IRE-1/XBP-1 pathway gene and they had a interactive effect. Conclusions: Exercise and diet modification had an good effect on NAFLD and the effect of exercise combined with diet modification was better, which may be related to the decrease of protein expression of PERK/eIF-2a and IRE-1/XBP-1 pathway gene and reducing endoplasmic reticulum stress.