Ethnopharmacological relevance: Kai Xin San (KXS), a traditional formula of Chinese medicine, has been used to treat dementia. Aim of the study: The present study aimed to investigate its ameliorating effects on A beta(1-40)-induced cognitive impairment in rats using a series of novel reward-directed instrumental learning tasks, and to determine its possible mechanism of action. Materials and methods: Rats were pretreated with KXS aqueous extract (0.72 and 1.44 g/kg, p.o.) for 10 days, and were trained to gain reward reinforcement by lever pressing at the meantime. Thereafter, rats received a bilateral microinjection of A beta(1-40) in CAl regions of the hippocampus. Cognitive performance was evaluated with the goal directed (higher response ratio) and habit (visual signal discrimination and extinction) learning tasks, as well as on the levels of memory-related biochemical parameters and molecules. Results: Our findings first demonstrated that KXS can improve A beta(1-40)-induced amnesia in RDIL via enhancing the comprehension of action-outcome association and the utilization of cue information to guide behavior. Then, its ameliorating effects should be attributed to the modulation of memory-related molecules in the hippocampus. Conclusion: In conclusion, ICXS has the potential to prevent and/or delay the deterioration of cognitive impairment in AD.