Objective To explore influencing factors of loperamide-induced constipation in mouse models by combining literature data mining and experimental research, to provide a reference for the establishment of a stable experimental constipation model. Methods Literature study, Constipation and animal model were used to search main titles, and then relevant literature from Chinese and English databases were retrieved. Then experimental studies were screened for mouse models of constipation induced by loperamide. Finally, data were extracted and analyzed by researchers. Experimental study, Male C57BL/ 6 mice were given 5 and 10 mg / kg loperamide orally once daily. We evaluated water content, timing of first melena and the intestinal propulsion rate to observe the effects of different doses and administration time of loperamide on mice with constipation. Results Literature study, We included 69 articles that met the standards, among which it was found that loperamide was mostly administered at doses of 5 and 10 mg / kg, with multiple intragastric administrations, the frequency of administration was once, and time of administration was mostly 30 min. Experimental study: From the day 1 of modeling, the water content of the 5 and 10 mg / kg groups significantly decreased (P< 0. 05) compared with the blank group. From day 7 to 14 of modeling, the water content of the 5 mg / kg group was significantly increased compared with the 10 mg / kg group (P< 0. 05). Comparison of changes in water content at 3, 7 and 14 days after modeling showed that the water content in each model group increased 1 day after drug withdrawal, and remained at high levels at 14 days after drug withdrawal. The timing of the first melena between day 7 and 14 of modeling was significantly increased (P< 0. 05) in the 5 and 10 mg / kg groups compared with the blank group. There were no significant differences in small intestinal propulsion rates among all groups ( P> 0. 05). Conclusions In the immediate effect experiment, loperamide was administered to mice for one time constipation modeling. For long-term intervention experiments, we can choose to treat mice with 10 mg / kg loperamide on the third day of modeling, and continue administration of loperamide to maintain the stability of the model.