This paper follows the diplomatic communication of Dubrovnik Republic with papal Rome, the Kingdom of Naples, Venice and its eastern Adriatic officials, regarding the appearance of plague cases in central and southern parts of Italy, but also on the eastern coast of the Adriatic, starting from 1656 to 1660. Although the Republic was spared in that period, already in 1656 the current difficult epidemiological situation of Rome and Naples had its direct repercussions on Dubrovnik Republic. Namely, the health supervisors of the most important papal port, Ancona, whether due to extreme precautionary measures or some other reason, suspended trade with the Republic due to the entry to Dubrovnik of five ships directed from the plague Naples. That news was also sent to Venice, so Dubrovnik government should have made a diplomatic effort to reject any doubts regarding the commone health in the Republic, then to re-establish undisturbed trade with these two very important Adriatic ports. Since the news of the plague in Rome and Naples did not abate, through the constant correspondence with its agents, Republic followed with a great interest the news regarding the spread of the current infection, primarily because of the prompt reaction, in order to protect the commone health, also its economic interests. The mentioned epidemic with all its potential dangers, as well as the accompanying blockade, happened during the Candian War, which kept the Dubrovnik government extremely vigilant, trying to prevent, among other things, any lack of food supplies due to the war-blocked usual supply routes. During the Candian War, especially in periods of plague epidemics - as well as in the specific cases followed by this paper - a motif of good and responsible government is omnipresent within diplomatic mail, otherwise existing in Dubrovnik’s public and political discourse since the humanism. Responsible governance presupposed the provision of optimal conditions for survival. As the basic postulate of every rule, including this one in Dubrovnik, responsible government justified the very fact of the acquired legitimacy of power, which came from God himself. Unlike other imagological motives, such as the most common one that referred to the Republic as a “wall of Christianity”, used so often tendentiously to gain support for certain own initiatives, or to justify various forms of “politically incorrect” behavior, this one that referred to the Dubrovnik sanitar experience had a real base in the strict practice of the health policy that Dubrovnik Republic tryed to implement for ages. As a strong argument Dubrovnik government referred to the only recent case, that one from the summer of 1647, when the territory of the Republic was directly endangered by the plague. This case Republic was presented as a bright example of successful dealing with such a serious threat. Such a confident performance of the Dubrovnik government represents a rare moment within its most often servile diplomatic discourse. This approach was simply necessary, both to confirm the integrity of Dubrovnik’s sanitary policy and to prevent negative economic effects, as any discreditation prevented Dubrovnik ships to access foreign ports. Rumors of the plague tended to spread as a fake news for several reasons: to prevent incursions from neighboring, hostile territory, such was a case from the summer of 1659, followed by this paper, when the Ottomans spread rumors about plague in Ottoman Albania trying to prevent looting incursions of Venetian land and naval troops. In this regard, the paper follows the cases when Dubrovnik ships had difficulty in accessing, primarily Ancona, under false accusations regarding the health of their crews, which can be justified in part as a result of great caution against any potential infection, but such actions also can be interpreted as reaction of the Italian trading milieu to the serious competitiveness of the neutral Dubrovnik flag during the Candian War. Other cases followed by this paper are reflecting two levels of active engagement against epidemics. The most direct one presupposed a strict series of precautionary measures as well as the even stricter quarantine ones practiced by the Dubrovnik Republic. Its equally active role was within a network that supported a sense of collective responsibility. It presupposed the transmission of any information regarding the spread of the disease in a particular area, for the sake of broader, joint coordination in order to prevent the inconceivable consequences that any epidemic could leave behind, as any plague epidemic didn`t stopped at the certain state borders.