Abstract: Objective: To observe the anti-anxiety effect of the water extracts of the mixture of Ziziphi Spinosae Semen (SZS) and Poria cocos (PC) with different ratios and to investigate the mechanism. Methods: Sixty-four SD rats were randomly divided into 8 groups, paroxetine group, SZS group, PC group, and the extracts with the different ratios of SZS to PC, which ranged from 1:1, 2:1 to 3:1. The anxiety model was established by chronic restraint and solitary which lasted for 28 days. During this period, the basic morphological features and body mass were observed. After 8 days of this treatment, paroxetine and different extracts were administrated. Elevated plus maze (EPM) and the open field test (OFT) were used to examine potential anxiolytic effects. It was determined by ELISA and quantitative real-time PCR for the total amount of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in serum, hippocampus, and amygdala tissues of rats, and the relative amount of mRNA expression. Results: Compared with the control group, the experimental groups that employed different proportions of SZS and PC could effectively improve the condition of morphological features, body mass, dysphoric behavior and regulate the level of inflammatory factors in serum and tissues (P<0.05, P<0.01). Among them, the combination of SZS-PC 3:1 could significantly improve the body weight of animals after 28 days of modeling (P<0.01). This treatment increased the total time of arm penetrations. At the same time, the ratio of the times of rats to enter the open arm was elevated. So was the ratio of the open arm stay time in the elevated plus-maze (P<0.01). And this treatment increased horizontal and vertical movements in the open field (P<0.01). Meanwhile, this treatment decreased the levels of inflammatory factors TNF-α, IL-1β, IL-6 (P<0.01), and mRNA expressions in serum, hippocampus, and amygdala tissue of rats (P<0.05, P<0.01). To sum up, the 3:1 group was better than SZS-PC 1:1 or 1:2 compound and SZS or PC alone. Conclusion: The combination of SZC and PC could effectively improve the condition of the treated rats, which includes the morphological features, body mass, and behavioral features. And the best group was 3:1 (SZS to PC). The mechanism of its anxiolytic effect might be related to the reduced levels of inflammation in peripheral and central areas.