OBJECTIVE： To investigate the effects of ligustrazine combined with N-acetylcysteine （NAC） on the peripheral pro-inflammatory cytokines and intestinal microflora of chronic stress rat. METHODS： Normal rats were included in normal control group， and chronic stress model rats were divided into model group， NAC group （60 mg/kg） and ligustrazine+NAC group （15   mg/kg+60 mg/kg）， with 20 rats in each group. They were given relevant medicine intragastrically for 15 d. The general inspection of rats were recorded in each group. Level of IL-6， IL-1β， TNF-α and INF-γ in serum were detected， and intestinal microflora was measured. RESULTS： Compared with normal control group， chronic stress symptom of rats were found in model group， and level of IL-6， IL-1β， TNF-α and INF-γ in serum were enhanced； Escherichia coli and Enterococcus in intestine were increased， while Bacterium lacticum and Bacillus bifidus were decreased （P＜0.05）. Compared with model group， chronic stress symptom of rats were relieved in NAC group and ligustrazine+NAC group， and above indexes were all improved （P＜0.05）； ligustrazine+NAC group was better than NAC group （P＜0.05）. CONCLUSIONS： Ligustrazine+NAC can improve chronic stress of rats by decreasing pro-inflammatory cytokines and improving the intestinal microflora.