[2] St. Paul's College was founded by Alessandro Valignano in 1594 by upgrading the previous Madre de Deus School, as a stopover to prepare Jesuit missionaries traveling east.

It had immense influence on the learning of Eastern languages and culture, housing the first western sinologists Matteo Ricci, Johann Adam Schall von Bell and Ferdinand Verbiest, among many famous scholars of the time.

In 2005, the ruins of St. Paul's – notably the facade of the Madre de Deus Church – were officially enlisted as part of the UNESCO World Heritage Site – Historic Centre of Macau.

To this end, he wrote to the Superior in India, who sent to Macau Jesuit scholar Michele Ruggieri (羅明堅)[4][5] who called the help of Matteo Ricci (利瑪竇), to share the work.

It was Valignano's first official act upon arriving in Japan that all new missionaries in the province spend two years in a language course, separating these newcomers by leaps and bounds from the first enthusiastic but stilted efforts of Francis Xavier.

In 1582, from Japan, Valignano sent an embassy[6] to the Pope and the kings of Europe sponsored by Kirishitan daimyos Sumitada, Ōtomo Sōrin and Arima Harunobu, whom he accompanied via Macau to Goa.

Between 1597 and 1762 it had immense influence on the learning of Eastern languages and culture by missionary Jesuits, making Macau a base for the spreading of Christianity in China and in Japan.

Its academic program soon became comprehensive and equivalent to that of a university: it included core disciplines such as theology, philosophy, and mathematics, geography, astronomy, and Latin, Portuguese and Chinese.

Many famous scholars taught and learned at this college, which became home to the first western sinologists such as Matteo Ricci, Johann Adam Schall von Bell and Ferdinand Verbiest.