Spleen is one of the main components of reticuloendothelial system and plays an important role in controlling of red blood cell quality with elimination of old and damaged cells. Physicians of Traditional Persian Medicine believed that spleen has a high incorporation with the liver, and liver has a main role in blood production. So its pathologic changes influence the production of hematologic elements in both aspects of amount and quality. In this study, chapters related to spleen disease in several Traditional Persian Medicine textbooks and available databases were reviewed. Further the relationship between anemia and spleen diseases were derived and evaluated. After interviewing two experts about the findings and reaching data saturation, the results were compiled and explained. Spleen dysfunction and diseases can lead to anemia, because of intercommunity with liver. This happens with different mechanisms such as: enlargement, cold distemperment, asthenia and crisis. Although there are many studies so far about anemia, but role of the spleen in the development of anemia is still not well known. Considering the role of the spleen in developing anemia, the drugs used in Persian medicine for spleen-originated anemia may provide an appropriate solution to treat the disease.