〔Abstract〕 Objective To explore the ameliorative effect of the endoplasmic reticulum stress inhibitor 4-phenylbutyric acid (4-PBA) on bile acid metabolism disorders induced by bacterial lipopolysaccharide (LPS) in late-pregnant mice, and to clarify the regulatory mechanism of endoplasmic reticulum stress (ERS) in intrahepatic cholestasis of pregnancy (ICP). Methods Twenty-four pregnant mice were divided into control group, LPS group, 4-PBA group, and LPS+4-PBA group. On the 16th day of pregnancy, the LPS group received intraperitoneal injection of LPS (200 μg/kg) and the 4-PBA group received injection of 4-PBA (150 mg/kg). In the LPS+4-PBA group, 4-PBA was intraperitoneally injected first, followed by LPS administration 1 h later. Serum total bile acid (TBA), liver injury markers, bile acid profiles, and the expression of key genes and proteins were detected 6 h after LPS treatment. Results LPS exposure increased serum TBA levels in pregnant mice(P<0.05), activated ERS markers and inflammatory factors, and downregulated bile acid transporters and the expression of the rate limiting enzyme CYP7A1(all P<0.05). 4-PBA intervention effectively inhibited ERS, reduced TBA levels(P<0.05), and upregulated Ntcp, Bsep, Mdr3, and Mrp3 gene expression(all P<0.05). Conclusion ERS plays an important role in LPS interference with the homeostasis of bile acid metabolism during pregnancy. Inhibiting ERS can improve bile stasis by regulating bile acid transporters, providing a theoretical basis for targeted therapy of ICP.