She is one of the earliest known women printmakers, making mostly reproductive engravings of well-known paintings or drawings, especially those of Raphael and Giulio Romano, or ancient Roman sculptures.

[citation needed] The cultural changes associated with the Italian Renaissance were providing women greater opportunities to study art,[2] and it became possible for female artists to gain international reputations.

She was regarded as a keen business woman, and one of the few women artists whom Vasari mentioned in the 1568 edition of his Lives, noting that she "engraves so well that it is a thing to marvel at; and I who saw her, a very gentle and gracious girl, and her works, which are most beautiful, was struck with amazement.

[5] Applying for a papal privilege was a fairly unusual practice before the papacy of Gregory XIII, especially for women, and it allowed her to establish a name for her household.

Resembling a book-printing privilege, it is about 300 words in length and names Diana as "wife of Franciscus Cipriani the architect, who is staying in this our alma Urbe ..." and indicates that she learned her art from her father.

Of this, one third would have gone to the Pope in office, one third to Diana, and the final third to the judge who issued the decision, naturally encouraging a judgment in favor of the artist.

Between 1576 and 1580, she made four prints featuring column capital volutes and other architectural details, including “bead and reel” and “egg and dart” moldings.

One relatively lengthy inscription on the earliest dated of these four prints further supports this interpretation: "This volute and old composite capital order of a numidian stone column, from St Peter in Vaticano for the Baptistry of Saint Peter was recorded by Francesco da Volterra in order to be useful to these artists for study.

[3] To celebrate the husband-and-wife artists admitted to the Congregazione dei Virtuosi del Pantheon, a pair of medallions were created.

The inscription on the obverse side of the medal, where she is shown with a matronly veil, simply says “Diana of Mantua.” The absence of her father's or husband's name was unusual for the time.

The figures of Christ and the young woman are depicted framed by the twisting Solomonic columns in the portico of a round temple.

In a letter to Eleonora, Diana says: "To her Serene Highness Lady Eleonora of Austria, Duchess of Mantua/ Diana Manuan/ I feel myself so tied to the memory of Your Ladyship’s most fortunate dominion, under which I possess, that to satisfy in par the gratitude in my soul I have been so bold as to bring this work of mine to light under her great name, in order that, returning to where it had its beginning, it serves her prince again, as a token of my service to Your Highness and your most serene house.

This work depicts the moment when Christ appoints Peter as head of the church in the Gospel of Matthew, which was a popular subject for the time.

Latona Giving Birth to Apollo and Diana on the Island of Delos was produced during her early career in Mantua.

It depicts Latona, the lover of Jupiter and protector of the nymphs, after giving birth to twins Apollo and Diana.

This signature also served to reference Mantuan nobility and the engraving tradition of Mantua which would mean more to influential people in Rome than the surname with which she was born.