Our previous study indicated that the water layer present in Fructus Schisandra(FSw) at 10 and 25 mg kg−1significantly counteracted cycloheximide (CXM)-induced amnesia. Therefore, the mechanism of action of the ameliorating effect of FSwon CXM-induced amnesia in the passive avoidance task was investigated in rats. The ameliorating effect of FSwon CXM-induced amnesia was depressed by scopolamine. The serotonin releaser, p -chloroamphetamine significantly antagonized the ameliorating effect of FSwon CXM-induced amnesia. Furthermore, the ameliorating effect was also inhibited by the 5-HT1Areceptor agonist 8-OH-DPAT, but potentiated by the 5-HT2receptor antagonist ritanserin. Finally, the GABAAreceptor antagonist bicuculline blocked the ameliorating effect of FSw. These results suggest that the beneficial effect of FSwon CXM-induced amnesia is amplified by treatment with serotonergic 5-HT2receptor antagonists, but reduced by serotonergic 5-HT1Areceptor agonists as well as GABAAand cholinergic receptor antagonists.