This study aimed to investigate the potential of Quercetin (Que) in ameliorating nonalcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) through the modulation of endoplasmic reticulum stress (ERS) in rats. After 8 weeks of HFD feeding, rats were randomly assigned to the following groups: HFD group, HFD + low-dose Que group (25 mg?kg-1), and HFD + high-dose Que group (50 mg?kg-1). The Control group consisted of rats fed a standard chow diet. After 16 weeks, rats were euthanized, and liver tissues and blood were collected for histological, biochemical, gene, and protein expression analyses. Throughout the experiment, no significant differences in food intake and body weight were observed among the four groups.Compared to the Control group, the HFD group exhibited increased serum levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), glutamic oxalacetic transaminase (AST), and glutamic-pyruvic transaminase (ALT), along with decreased high-density lipoprotein-cholesterol (HDL-c) levels (P<0.05). In the low-dose Que group, serum levels of TG, TC, LDL-c, AST, and ALT were significantly reduced compared to the HFD group (P<0.05). Similarly, the high-dose Que group showed decreased serum levels of TG, TC, AST, and ALT compared to the HFD group (P<0.05). In the HFD group, the liver exhibited enlargement and increased absolute weight, with prominently swollen hepatocytes, marked vacuolization, and accumulated lipid droplets. Additionally, increased collagen deposition, insulin resistance, and impaired glucose tolerance were observed in the HFD group. However, these alterations were reversed in both low- and high-dose Que groups. Quantitative polymerase chain reaction (Q-PCR) results demonstrated that Que treatment significantly suppressed the expressions of several ERS-related genes, including bip, atf6, atf4, xbp-1s, and chop (P<0.05 or P<0.01). Furthermore, Western blot analysis revealed that Que substantially suppressed the protein expressions of ATF4, ATF6, XBP-1s, BiP, and CHOP, which were upregulated in the HFD group (P<0.05). Overall, our findings indicate that Que treatment attenuates HFD-induced aberrant lipid metabolism, impaired glucose tolerance, and hepatic lipid deposition in NAFLD rats, with modulation of the ERS-related pathway potentially playing a critical role.