Melatonin improved amygdala-dependent emotional memory in Tg2576 mice. Melatonin increased the expression of c-fos protein levels in basolateral amygdala. Melatonin increased the expression of pCREB/CREB ratio in basolateral amygdala. CREB/c-Fos pathway play critical role for the efficacy of melatonin in Tg2576 mice.