Abstract： Objective： To study the effect of Xiaoyao powder on dual- specificity phosphatase 14(DUSP14) mRNA expressions and four types of mitogen-activated protein kinases(MAPKs) signaling pathways in the activated state，namely p38 mitogen- activated protein kinase(p38 MAPK)， c- Jun N terminal protein kinase(JNK)， extracellular signal- regulated kinase(ERK) and extracellular signal-regulated kinase 5(ERK5)，in hippocampus of chronic stress rats. Methods：A total of 80 rats were divided into the blank group，the model group，the fluoxetine group and the Xiaoyao powder group. The blank group was routinely fed，and given 2 mL of normal saline by gavage every day；the model group was treated with chronic stress stimulation after being given 2 mL of normal saline by gavage every day；the fluoxetine group and the Xiaoyao powder group were treated with chronic stress stimulation after being given 10 mL/(kg · d) of fluoxetine and Xiaoyao powder by gavage respectively. The expressions of DUSP14 mRNA and the relative contents of p38，phosphorylated p38(p-p38)，JNK， phosphorylated JNK(p-JNK)，ERK，phosphorylated ERK(p-ERK)，ERK5 and phosphorylated ERK5(p-ERK5) in hippocampus of rats in each group were detected. Results：Compared with those in the blank group，DUSP14 mRNA expression in the model group was significantly up-regulated(P＜0.01)，p-p38/p38，p-JNK/JNK，p-ERK5/ERK5 were significantly increased (P＜0.01)，and p-ERK/ERK was significantly decreased(P＜0.01). Compared with those in the model group，DUSP14 mRNA expressions in the Xiaoyao powder group and the fluoxetine group were down- regulated(P＜0.01)；p-p38/p38 and p-JNK/ JNK in the Xiaoyao powder group were significantly decreased(P＜0.01)， and p- ERK/ERK was significantly increased(P＜ 0.01)； p-p38/p38 and p-JNK/JNK and p-ERK5 /ERK5 in the fluoxetine group were significantly decreased(P＜0.01)， and p-ERK/ERK was significantly increased(P＜0.01). Compared with those in the fluoxetine group，p- JNK/JNK and p- ERK5/ ERK5 in the Xiaoyao powder group were higher(P＜0.05，P＜0.01). Conclusion：Xiaoyao powder and fluoxetine have similar regulatory trend on the changes in DUSP14 mRNA expressions and activities of each MAPK signaling pathway caused by chronic stress， and similar regulatory effect on p38 MAPK signaling pathway， but Xiaoyao powder shows no activity regulation in ERK5 MAPK pathway，and fluoxetine shows more advantages in the regulating process of ERK and JNK MAPK pathways in the activated state.