Objective To compare and analyze differences between two modeling method of mouse pre-eclampsia (PE), and to provide a reference to select different types of PE animal models. Methods Overall, 24 CD-1 pregnant mice were randomly divided into LPS control, LPS, R848 control and R848 groups with six mice in each group. Saline or LPS (4 mg / kg) was injected intravenously via the tail vein into mice in LPS control or LPS groups on days 13 ~ 17 of pregnancy. R848 solvent or R848 (10 mg / kg) was injected intraperitoneally into mice of R848 control and R848 groups on days 13, 15 and 17 of pregnancy. Systolic blood pressure of the tail artery was measured on days 12, 14, 16 and 18 of pregnancy. The mice were dissected on day 18 of pregnancy, followed by urine protein / creatinine detection, anti-vascular generation factor detection, and HE staining. Results Compared with the control group, gestational hypertension occurred in both modeling method. Blood pressure on days 14, 16 and 18 of pregnancy in the LPS group was ( 142. 16±4. 81), (144. 07±2. 91), and (143. 31±4. 61) mmHg, respectively. Blood pressure on days 14, 16 and 18 of pregnancy in the R848 group was ( 154. 00 ± 5. 29), ( 147. 44 ± 3. 24) and ( 140. 77 ± 2. 00) mmHg, respectively. Urine protein / urine creatinine tests showed that the ratio was increased in the LPS model group ( P< 0. 05), but there was no statistical difference in the R848 group ( P> 0. 05). Compared with the corresponding control group, there was no significant difference in sFlt-1 or sEng expression in the lipopolysaccharide group (P>0. 05), whereas sFlt-1 and sEng expression was increased in the R848 group (P<0. 01). Compared with the control group, the R848 group had chronic injury of placental blood vessels, and extensive hyperplasia of syncytiotrophoblasts in pregnant mice. Conclusions Both modeling method induce symptoms of PE in pregnant mice, such as hypertension, fetal growth restriction, and endothelial dysfunction. However, the damage caused by the R848 modeling method is more serious and its advantage is a simple operation.