In 1508, the Tribunal del Santo Oficio of the Inquisition court was instituted. Obtained by the influence of the degree Luis Zapata, Director and Advisor to Isabella, it was aided by the existence of Jewish population in the lower Extremadura. It was the third Court of Spain, as regards the extension of its jurisdiction. It occupied 42.260 square kilometers, and included the bishoprics of Ciudad Rodrigo, Piacenza, Coria, and Badajoz. Occupying three headquarters in Llerena, the Priory Palace in Zapaterķa Street, the House maestral Street La Prison and finally, until its abolition in 1834, Palace of the Zapata, now justice in la Corredera Street today.
Its period of maximum splendor was in 16th century that had seven convents, as well as a great cultural activity. During this century there was a large population increase only diminished by certain emigration to the new world, becoming the second largest population centre of Extremadura in 1591 behind capital Badajoz. At the end of the century had 8,300 inhabitants.
In 1594, the census of population in the provinces and marches of the Crown of Castile in 16th century was part of the Leon province and had 2,066 neighbors, including its suburbs of Llerena such as Maguilla.In the year 1640, due to the growth it had achieved, Philip IV granted Llerena the title of City.