Objective To find a stable method for establishing a loperamide hydrochloride-induced slow transit constipation (STC) model by comparing the differences among STC mouse models established by different loperamide hydrochloride concentrations and administration times. Methods Healthy male C57BL/ 6 mice were given 0. 025, 0. 25 or 2. 5 mg / mL loperamide hydrochloride by intragastric administration twice a day at 9:00 and 15:00. The small intestinal propulsion rate, defecation quantity and other indicators were used to evaluate the effects of different doses and administration times on the STC mouse model. Results ( 1) Comparing the effects of different dosages of loperamide hydrochloride in the range of 0. 5 mg / kg to 50 mg / kg revealed that the small intestinal propulsion rate and defecation quantity significantly decreased in the 50 mg / kg dosage group compared with those in the control group (P < 0. 05). (2) At day 7 after oral administration of loperamide hydrochloride, the small intestinal propulsion rate significantly decreased compared with that in control group (P < 0. 05), whereas this rate did not significantly change at days 3, 10 and 14 (P> 0. 05). Conclusions The small intestinal propulsion rate and defecation quantity significantly decreased after continuous administration of 50 mg / kg loperamide hydrochloride for 7 days. Hence, this is a relatively stable method for establishing an STC mouse model. This study provides valuable data for the exploration of the loperamide hydrochloride-induced STC model.