To discuss the curative effect of Yishen Zhumian Tang combined with zolpidem on insomnia and its effect on neurotransmitters in the brain.Methods：A total of 110 patients with insomnia admitted to Wenzhou Hospital of Chinese Medicine from July 2017 to July 2018 were selected as research objects.The clinical data of all patients were analyzed by systematic retrospective analysis method.According to the different treatment methods in the data，all patients were divided into the control group and the study group，55 cases in each group.The control group was treated with zolpidem tartrate，and the study group was treated with Yishen Zhumian Tang combined with zolpidem tartrate.Both groups were treated for four weeks.Clinical effect，scores of Pittsburgh seep quality index(PSQI)，levels of neurotransmitters in the brain and the incidence of adverse reactions were compared between the two groups.Results：The effective rate of clinical treatment in the study group was 96.36%，significantly higher than that of 76.36%in the control group(P＜0.05).After treatment and two months after treatment，scores of PSQI in both groups were significantly decreased when compared with those before treatment(P ＜ 0.05).After treatment and two months after treatment，the PSQI score in the study group was significantly lower than that in the control group(P ＜ 0.05).After treatment，the levels of γ-aminobutyric acid(GABA)in the two groups were significantly higher than those before treatment(P ＜ 0.05)，and the GABA in the study group was significantly higher than that in the control group after treatment(P ＜ 0.05).After treatment，the level of 5-hydroxytryptamine(5-HT)in the study group was significantly higher than that in the control group(P＜0.05).The incidence of adverse reactions in the study group was 3.64%，significantly lower than that of 14.55%in the control group(P＜0.05).Conclusion：The therapy of Yishen Zhumian Tang combined with zolpidem has significant therapeutic effect in treating patients with insomnia with high safety，whose mechanism may be related to increased levels of neurotransmitters such as GABA and 5-HT in the brain.