Abstract： Objective： To observe the clinical effect of Zengye Tongmi Prescription combined with Prucalopride Succinate Tablets on constipation with excess heat syndrome and its effects on serum substance P (SP)，vasoactive intestinal polypeptide (VIP) and nitric oxide (NO). Methods：A total of 60 cases of constipation with excess heat syndrome were divided into the control group and the treatment group according to the random number table method， with 30 cases in each group. The treatment group was given the oral administration of Prucalopride Succinate Tablets combined with Zengye Tongmi Prescription， and the control group was treated with Prucalopride Succinate Tablets. Before and after treatment， the scores of traditional Chinese medicine (TCM) symptoms and levels of serum intestinal neurotransmitters in both groups were compared， and the clinical effects and incidence of adverse reactions were also evaluated. Results：After treatment，the total effective rate was 93.33% in the treatment group，higher than that of 76.67% in the control group (P＜0.05). After treatment， the scores of symptoms， including abdominal detention and pain，defecation time，dry and solid stool in nature and dry mouth and thirsty in the two groups were lower than those before treatment (P＜0.05)， and the above four TCM symptom scores in the treatment group were lower than those in the control group (P＜0.05). After treatment，the SP levels in both groups were higher than those before treatment (P＜0.05)， the levels of VIP and NO were lower than those before treatment (P＜0.05)， and the VIP and NO were lower than those in the control group (P＜0.05)，and the SP was higher than that in the control group (P＜0.05). No adverse reactions were observed in the two groups. Conclusion： Zengye Tongmi Prescription combined with Prucalopride Succinate Tablets has a definite curative effect on constipation with excess heat syndrome， which can effectively regulate the levels of intestinal neurotransmitters of patients and mitigate the constipation symptoms，with no adverse reactions.