Republic of Ragusa was an active merchant city-state and was thus in a contact with people and goods from all over the world so it had to introduce preventive health measures to protect its citizens from various epidemics which broke out in countries across the Mediterranean and the Balkans due to poor hygiene.

Given that the preparations for the treatment of various infectious diseases recommended by the doctors at the time, such as vinegar, sulfur and garlic, were ineffective, people came up with the idea of stopping epidemics from spreading by isolating the infected.

[citation needed] On 27 July 1377, the Great Council of the Republic adopted a decree which introduced a quarantine as a measure of protection against the spread of infectious diseases by which all merchants, sailors, and goods arriving from "suspicious lands" could not enter the city if they haven't spent a month in a quarantines which were on the remote, uninhabited islands of Mrkan, Bobara and Supetar.

This decree was published in Dubrovnik's book of laws, the so-called Green Book (Latin: Liber viridis); Veniens de locis pestiferis non intret Ragusium nel districtum (English: Whoever comes from the infected lands shall not enter Ragusa or its territory).

The penalties for not complying with the provisions of this decree were 100 ducats or prison sentence and severe corporal punishment.

By the mid-15th century, quarantines have become complex institutes that employed scribe, two guards, gravedigger, two cleaners, and additionally, since 1457 epidemic, priest, barber and two kacamortis.

[6] After the fall of the Republic in 1808, lazarettos were used for quarantine of merchants coming to Dubrovnik from the inner-Balkans, and later for military purposes.

At first, three courtyards and a number of covered porches and dwellings for the ship crew members and caravan companions were built.