〔Abstract〕 Objective To investigate the protective effect of obeticholic acid(OCA) on di(2-ethylhexyl) phthalate(DEHP)-induced cholestasis in mice. Methods Animal experiment 1: Female ICR mice were randomly divided into 3 groups: the control group, DEHP low-dose group [50 mg/(kg·d)]and DEHP high-dose group [200 mg/(kg·d)]. All mice were administered with DEHP by gavage for 18 days. Animal experiment 2: Female ICR mice were randomly divided into 4 groups: the control group, OCA group, DEHP model group[200 mg/(kg·d)]and DEHP+OCA group. All mice were administered with DEHP by gavage for 18 days and the duration of OCA was 12-18 days. Serum and liver tissues of mice were collected. Serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bile acid(TBA) levels, liver TBA levels, protein expression of farnesoid X receptor(FXR) and mRNA levels of FXR and SHP were detected. HE staining was used to observe the pathological changes in liver tissues. Results Experiment 1: Compared with the control group, the liver weight, liver coefficient and the TBA concentrations in serum and liver significantly increased only in DEHP[200 mg/(kg·d)] group(P<0.01), indicating that the modeling was successful. Animal experiment 2: Compared with the DEHP model group, the liver weight and liver coefficient significantly decreased after OCA treatment, and the TBA concentrations in serum and liver both decreased(P<0.01). Compared with the control group, the protein expression level and its mRNA level of FXR decreased after DEHP[200 mg/(kg·d)]treatment; Compared with the DEHP model group, the protein expression of FXR and the mRNA levels of FXR and SHP significantly increased after OCA treatment(P<0.05). Conclusion DEHP exposure can induce cholestatic liver injury in mice, and OCA posttreatment has a protective effect on DEHP-induced cholestasis in mice.