In 1532 Pflug became dean of Zeitz, where he had to grapple with the practical question of the Reformation, since not only was the bishop, who was also diocesan of Freising, continually absent, but the neighboring Protestant elector of Saxony was alleging claims of jurisdiction over the See.
He took part in the Leipzig Colloquy in 1534, and as dean of Meissen prepared for the clergy of the diocese the constitutions reprinted in the Leges seu constitutiones ecclesiœ Budissinensis (1573).
As one of the envoys of John of Meissen, Pflug endeavored, in 1539, to secure from the papal nuncio, Alexander, who was then at Vienna, adhesion to his project for a reform of Roman Catholicism along the lines already indicated, only to be obliged to wait for the decision of the pope.
He took part in negotiations in Pegau, continuing them in a secret correspondence with Melanchthon to induce him and Prince George of Anhalt to accept a modified sacrificial theory of the Mass; and he was also concerned in the deliberations between Maurice and Joachim II and their theologians at Jüterbog.
In his own diocese Pflug refrained from disturbing the Lutherans, restoring Roman Catholic worship only in the chief church in Zeitz and the cathedral of Naumburg, and even permitting Protestant services to be held in the latter.
Even after the final success of the Protestants in 1552, he remained in undisturbed possession of his see, thanks to his popularity and moderation; and after the abdication of Charles V, he urged the best interests of Germany in his Oratio de ordinanda republica Germaniœ (Cologne, 1562).