Much of his early education was outside of Venice, accompanying his father who was an active politician and diplomat. He received further education in Verona with an uncle, also named Ermolao. In 1462 he was sent to Rome, where he studied under Pomponius Laetus and Theodorus Gaza. By 1468 he had returned to Verona, where Frederick III awarded him a laurel crown for his poetry.
He completed his education at the University of Padua, where he was appointed professor of philosophy there in 1477. Two years later he revisited Venice, but returned to Padua when the plague broke out in his native city.
Barbaro had an active political career, though he resented these duties as a distraction from his studies. In 1483 he was elected to the Senate of the Republic of Venice. He was twenty when he gave the funeral oration for Doge Nicholas Marcello. In 1486, he was sent to the court of the Duchy of Burgundy in Bruges. In 1488 he held the important civil post of ‘’Savio di Terrafirma’’. In 1489 he was appointed ambassador to Milan and in 1490 he was appointed Ambassador to Rome. In 1491, Pope Innocent VIII, nominated him to the office of Patriarch of Aquileia.
It was illegal under Venetian law for ambassadors to accept gifts or positions of foreign heads of state. There was also a dispute between Venice and the Papacy as to who should nominate Patriarchs of Aquileia. Barbaro was accused of treason and the Venetian Senate ordered him to refuse the position. Pope Innocent and his successor Alexander VI threatened to excommunicate Barbaro if he resigned as Patriarch of Aquileia.
The Venetian Senate revoked Barbaro’s appointment as ambassador and exiled him from Venice. They threatened the same for his father, Zaccaria, as well as confiscation of both men's property, but Zaccaria died shortly afterwards.
Barbaro then lived in a Roman villa on the Pincian Hill belonging to his brothers Daniele and Ludovico. He died there of the plague in 1493 and was buried at the church of Santa Maria del Popolo. Ferdinando Ughelli mentions an inscription to Barbaro there, but it was lost by 1758. Valeriano wrote a tribute to Barbaro.
Barbaro edited and translated a number of classical works: Aristotle's Ethics and Politics (1474); Aristotle's Rhetorica (1479);Themistius's Paraphrases of certain works of Aristotle (1481);Castigationes in Pomponium Melam (1493).
His own work, De Coelibatu was less influential, but Barbaro's Castigationes Plinianae, published in Rome in 1492 by Eucharius Silber, was perhaps his most influential work. In this discussion of Pliny's Natural History Barbaro made 5000 corrections to the text. The work was written in only twenty months and dedicated to the newly elected Pope Alexander VI. Castigationes Plinianae was considered by Barbaro's contemporaries to be the most authoritative work on Pliny. Even before his death, he was considered a leading authority on the Greek and Latin works of antiquity. Erasmus frequently cited Barbaro's works, often with respect.
His letters to Giovanni Pico were also widely circulated. Much of his work was published after his death: In Dioscuridem Corelari, a work on Dioscorides, in 1510, his translations of Aristotle in 1544, and Compendium Scientae Naturalis in 1545.
Barbaro's work De Officio Legati was representative of a revolution in the conduct of diplomacy which took place during the Renaissance.
- Erasmus and Fisher: Their Correspondence 1511-1524, Vrin, 1968, p. 90. The Cambridge History of Italian Literature (Cambridge University Press, 1999, p. 148) gives 1453/4.
- Gaisser, Julia Haig; Pierio Valeriano 'Pierio Valeriano On the ill fortune of learned men: a Renaissance humanist and his world Ann Arbor: University of Michigan Press 1999. p.288 ISBN 0-472-11055-1
- Bietenholz, Peter G. Contemporaries of Erasmus a biographical register of the Renaissance and Reformation, v.1-3, A-Z Toronto; Buffalo: University of Toronto Press 2003. pp.91–92 ISBN 0-8020-8577-6
- Michaud, J. Fr. ; Louis Gabriel Michaud Biographie universelle, ancienne et moderne Paris: Michaud 1811-28. p.329
- Rose, Hugh James; Henry John Rose A new general biographical dictionary, Volume 3 London: Fellowes et al. 1857. p.137
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- Chisholm, Hugh, ed. (1911). "Barbaro, Ermolao". Encyclopædia Britannica (11th ed.). Cambridge University Press.