Abstract: In the Safavid era, 1501-1722, Iran faced interrelated political, religious, social, economic and cultural changes. Accordingly, without consideration of these factors, nothing in the Safavid society could be studied or analyzed. Concurrency of these developments with the culmination of evolutions in Europe, the presence of Europeans in different scenes of Iran’s community and neighborhood with the Ottomans added to the complexity of the description and interpretation of the evolutions during this period. Despite these complexities, the art especially the art of the book layout, as a mirror displaying the complete changes in society, is an efficient tool for understanding and interpreting the developments. So, investigating many factors such as religion, politics, foreign relations, cultural exchange as well as Safavid king’ interest to art, through a library-analytical method, it was concluded that these factors had contributed to the development of arts, particularly the art of book layout. In addition, the mentioned factors were effective on changing the style and decline of the book layout.