Objective To compare the rat model of slow transit constipation (STC) established with gavage or feeding compound di-phenoxylate. Methods Forty Sprague-Dawley rats were randomly divided into gavage control group (A), gavage group (B), feeding control group (C) and feeding group (D) equally. Group B was given compound diphenoxylate suspension by gavage for 14 days while group A ac-cepted isodose normal saline. Group D were given feed containing compound diphenoxylate for 120 days while group C accepted normal feed. Carbon ink was poured into stomachs to observe the propelling rate after modeling, and the content of aquaporin 3 and aquaporin 4 were detected with immunohistochemistry. Results There were two rats died in group A and group B, respectively. The carbon ink propel-ling rate was lower in group D than in group B (P<0.05). Both aquaporin 3 and aquaporin 4 were more in group D than in group B (P<0.05). Conclusion STC rat model can be established by eating diphenoxylate feed for 120 days, which is safer and more stable than that of gavage for 14 days. Aquaporins in colons may play a role in onset and development of STC.