In 1757 Orfelin became the secretary to Metropolitan Pavle Nenadović in Sremski Karlovci, the Serbian political and spiritual centre at the time. Metropolitan Pavle wanted to establish Karlovci as an independent educational centre and evade Imperial Austrian control over censorship. In collaboration with Zaharije Orfelin, he founded the "Copper Publishing House", where the first modern Orthodox literary works and a considerable number of prints were made. Soon Orfelin began publishing poems, translating books, and creating etchings and engravings, inspired by the work of his contemporaries. To fulfill his ambition to print more books, he moved to Venice where he founded and edited the first Serbian review, "Slaveno-Serbski Magazin" (1768). Poem "Plač Serbii Lament of Serbia" and biography of Peter I of Russia "Istorija o žitija i slavnih djelah velikago gosudarja i imperatora Petra Pervago" are considered his most notable works. His "Slaveno-Serbski Magazin" paved the way to the Slavonic-Serbian language. He was the first to publish in the 18th century texts pertaining to Serbian social and cultural history when other European nations had yet to entertain the subjects. During this period Orfelin first began to write "The Big Serbian Herbalium", in which he detailed the sanative effects of 500 species of herbs. And, in the "Experienced Winemaker" he listed several hundreds of recipes for preparation of herbal wines and other potions. Orfelin was fluent in Russian, Latin, German, and French.