One of the biggest achievements of the second half of the last century, in the field of medicine, was the antibiotics development. Today, their uncontrolled and inappropriate usage is considered as a huge public health problem, because of the occurrence of antibiotics resistance resistance of microorganisms to antimicrobial agents. Around 50% of the antibiotics prescribed during the hospitalization period of the patients are unnecessary or inappropriate. Endemic forms of occurrence and maintenance of resistant and multiresistant bacteria in hospitals, especially in intensive care units, increase morbidity, treatment costs and mortality of hospitalized patients. Aim: To confirm the information and knowledge of the antibiotics usage and antibiotics resistance among the population of the eastern region of Republic of North Macedonia. Material and Methods: The paper is a transphase study conducted in the period from 01.10.2018 30.11.2018 on the territory of the municipalities of Stip, Probistip, Kocani, Radovis and Strumica. Fur fulfilling the set goals, a specially designed questionnaire was made, and a total of 526 respondents fulfilled it voluntarily and anonymously. The descriptive and the analytical epidemiological method of work were used. Results: From the total number of 526 respondents, 230 (43,7%) were men, and 296 (56,3%) were women. The respondents were on the age from 18 to 70 years. 385 (73,2%) of them live in a city. The female population take antibiotics with a doctor's recommendation more in comparison with the male population. More than 50% of the respondents confirmed that the antibiotics affect both bacterias and viruses. 98 (42,6%) of the men, and 264 (56,1%) of the women responded that they are aware what antibiotics resistance is. From the total number of 264 respondents who said that know about antibiotics resistance, only 127 (48,1%) indicate that the doctors and tge pharmacists as the source of information. Conclusion: The population of the eastern region of our country is not informed enough for antibiotics usage and the antibiotics resistance. The information that only 127 (24,1%) respondents of a total number of 526 respondents has gained their information from doctors and pharmacists is worrying. The main reason for appearing of resistance to bacteria is excessive and unconscious use of antibiotics, their unnecessary consumption, discontinuation of the treatment before it is completed, taking inadequate (smaller) doses than necessary and disregarding the correct intervals when taking therapy.