This study presents and discusses first detailed petrographic, microthermometric and Raman spectroscopic data from quartz-hosted fluid inclusions at Rudnik Zn-Pb-Cu-Ag skarn deposit (Serbia) and combines them with the information on skarn- and ore paragenesis. Three periods in the metamorphic-hydrothermal history of the deposit are recognized: 1) the pre-ore prograde skarn period when garnet-clinopyroxene skarns formed, 2) the syn-ore period that encompasses a retrograde stage marked by epidote and zoisite and a quartz-sulfide stage characterized by quartz, pyrrhotite, sphalerite, galena and chalcopyrite, and 3) the post-ore period associated with precipitation of calcite and quartz. The hydrothermal evolution is inferred from studying six groups of quartz-hosted fluid inclusions (FI). Two-phase FI of high- (Group A) and moderate salinity (Group B) are found in quartz cores and homogenized at 380–390 °C (mode) and 370–380 °C (mode), respectively. Group A FI consists of H ₂O-NaCl liquids and CO ₂-CH ₄ gas mixtures and likely represents the original fluid composition, whereas Group B FI records dilution of the original fluid at constant temperature, with a slight increase in CH ₄ contents. The quartz cores also contain Group C as volatile-rich FI (mostly CO ₂ with up to 10 mol% CH ₄ and H ₂S) of a moderately low salinity and liquid-rich Group D FI composed of pure water with homogenization temperatures of 180–200 °C (mode). The transitional zones of quartz crystals show overgrowth textures and host Group E FI with low salinity that homogenized at 235–401 °C, which vapour phase is a CO ₂-CH ₄ mixture with up to 17 mol% CH ₄. Group F comprises FI found within the rim zones of quartz crystals and they exhibit a low salinity and homogenization temperatures between 259–365 °C. Accordingly, the hydrothermal history at Rudnik involved: a) mixing of different salinity fluids at high temperatures (Groups A and B—retrograde stage), b) introduction of fluids with high volatile contents (Group C) and cooling of fluids with constant salinity (between Groups E and F), which likely correspond to the quartz-sulfide stage, and c) inflow of meteoric water (Group D—the post-ore quartz-calcite stage).