Abstract：Objective：To observe the clinical effect of the therapy of Suanzaoren tang combined with eszopiclone tablets on patients with primary insomnia and its influence on bad mood，sleep quality and safety. Methods：A total of 80 patients with primary insomnia were divided into the control group and the study group according to the random number table method， with 40 cases in each group. The control group was treated with eszopiclone tablets， and the study group was treated with Suanzaoren tang combined with eszopiclone tablets. The total effective rates and incidence of adverse reactions in the two groups were compared. Before and after treatment，the scores of SPIEGEL Scale，Pittsburgh Sleep Quality Index (PSQI)， Hamilton Anxiety Rating Scale(HAMA) and Hamilton Rating Scale for Depression(HAMD) and serum levels of γ- amino butyric acid(GABA)，substance P(SP) and brain-derived neurotrophic factor(BDNF) in the two groups were compared. Results：The total effective rate was 92.50% in the study group，higher than that of 75.00% in the control group(P＜0.05). After treatment， the scores of SPIEGEL， PSQI， HAMA， and HAMD and serum levels of SP in the two groups were decreased when compared with those before treatment(P＜0.05)，and the serum levels of GABA and BDNF were increased (P＜0.05)；the scores of SPIEGEL，PSQI，HAMA，and HAMD and serum levels of SP in the study group were lower than those in the control group(P＜0.05)，and the serum levels of GABA and BDNF were higher(P＜0.05). There was no significant difference being found in the comparison of incidence of adverse reactions between the two groups(P＞0.05). Conclusion： The therapy of Suanzaoren tang combined with eszopiclone tablets has a significant clinical effect on primary insomnia，which can reduce the bad mood，improve the sleep quality，and regulate the serum levels of GABA，BDNF and SP，with good safety.