The present invention “use of Maitake and Maitake polysaccharide D Fraction in manufacture of medicaments for anti-depression” belongs to the field of pharmaceuticals, which characterized in that the Maitake whole herb, Maitake extract or Maitake polysaccharide D fraction is used in the preparation of antidepressants. The medicament can be used to treat or prevent depression, which has a significant antidepressant effect, not only strong effect, but also no conventional antidepressant medicaments toxicity, side effects, such as induced epilepsy, ataxia and other shortcomings. Therefore, they can be used as an excellent antidepressant candidate medicament.