Abstract：Objective：The purpose of this study is to verify whether the mechanism of ginkgolide B (GB) in the treatment of metabolic associated fatty liver disease (MAFLD) is related to the regulation of the PERK/ eIF2α/ATF4/CHOP signaling pathway to inhibit endoplasmic reticulum stress and alleviate hepatocyte apoptosis and inflammation through animal experiments. Methods： A total of 72 male SD rats were randomly divided into normal group，model group，Simvastatin group and GB low-，middle- and highdose (GB-L，GB-M and GB-H) groups (n=12). Except for the normal group，the other groups were fed a high-fat high-sugar diet to establish animal models for 12 weeks. After 8 weeks， serum and liver tissue were collected. Biochemical kit was used to detect blood lipids ， liver lipids， [total cholesterol(TC)， triglyceride(TG)，high density lipoprotein cholesterol(HDL- C)，low density lipoprotein cholesterol(LDL- C)] and liver function [aspartate aminotransferase(AST)，alanine aminotransferase(ALT)]. Detect serum and liver inflammatory factors [interleukin- 1(IL-1)，interleukin- 6(IL-6)，tumor necrosis factor- α(TNF-α)] levels by enzyme- linked immunosorbent assay(ELISA). Observation of liver histopathology by HE and Oil red O staining. Detect protein expressions of GRP78， PERK，p- eIF2 α，ATF4，CHOP，Bcl- 2 and Bax in liver tissue by Western blot. Results：Liver histopathology showed that hepatic steatosis in the model group were significantly higher than those in the normal group， and the condition were especially improved in all treatment groups. Biochemical indexes and protein expression showed that compared with the normal group，the levels of TC，TG，LDL-C，IL-1，IL-6 and TNF-α in liver and serum，AST and ALT in serum and GRP78，PERK，p- eIF2α，ATF4，CHOP and Bax in liver in model group were remarkably increased (P＜0.05)，the levels of HDL- C in liver and serum and liver Bcl- 2 were significantly decreased (P＜0.05). Compared with the model group，the levels of TC，TG，LDL- C，IL- 1，IL- 6 and TNF- α in serum and liver， ALT and AST in serum and GRP78， PERK， p- eIF2α， ATF4， CHOP and Bax in the liver in each treatment group were significantly decreased (P＜0.05)，while the level of Bcl- 2 in liver was significantly increased (P＜0.05). Compared with the model group， HDL- C levels in serum and liver of GB- H group were significantly increased (P＜0.05). HDL-C levels in GB-L and GB-M groups showed an up-regulated trend， but there was no statistical difference between the two groups and model group (P＞0.05). Conclusions：GB has a therapeutic effect on MAFLD. Its mechanism may be related to the regulation of the PERK/eIF2α/ ATF4/CHOP signaling pathway to inhibit endoplasmic reticulum stress and alleviate hepatocyte apoptosis and inflammation.