Sediment-hosted lead-zinc deposits in northwestern Guizhou, China, are located on the southwest margin of the Yangtze craton and Youjiang orogenic belt. They are hosted by Proterozoic and Paleozoic carbonate rocks along the Ziyun-Yadu Fault. The ore minerals include sphalerite, galena, and pyrite, with minor tetrahedrite.This study focus on mineralogy and geochemistry of ores, petrography, microthermometry, laser Raman spectroscopy and LA-ICP-MS analyses of fluid inclusions, and sulfur, lead, zinc isotopic compositions of sulfides are used to characterize the ore-forming fluids associated with Pb-Zn mineralization in the northwestern Guizhou, and to understand the formation of lead-zinc deposits in northwestern Guizhou, China. The results and conclusions are followings:1. The ore consists mainly of sphalerite, galena, and pyrite, with quartz, calcite and dolomite veins. The sphalerite and galena have high concentrations of Ag (68 to138ppm), As (3 to 1570 ppm), Sb (2 to 3840 ppm) and Se (20 to 1020 ppm) determined by eletron microprobe analysis (EPMA). Minor tetrahedrite containing As (3 to 20 wt%), Sb (6 to 20wt%), and Au (500 to 1000ppm) is the first indentified in some deposits and intergrows with sphalerite and galena or cutting sphalerite.2. Fluid inclusion studies show that the fluid inclusions in quartz are two-phase, aqueous inclusion and have higher homogenization temperatures (160～260℃) and salinities of 5～22 wt%NaCl equiv., with low density of CO2, CH4 and N2 vapor determined by Laser spectroscopy, whereas the homogenization temperatures of two-phase aqueous inclusions in sphalerite range from 160～180℃, with salinities of 3～23 wt%NaCl equiv. LA-ICP-MS microanalysis indicate that fluid inclusions in quartz contain high contents of Cl (14～38 wt %)、K (2184～78451 ppm), Cu (2～387 ppm), Pb (2～14043 ppm), Zn (12～4350ppm), As (4～1186 ppm), and Sb (1～99 ppm). The correlation of Cu, Pb, Zn and Cl suggests that these metals are transported by chlorine complexes. Hydrogen and oxygen isotopes (δ18OH2O=1.8‰～17.0‰，δD=-46‰～-55‰) suggest derivation from metamorphic water.3. Sulfur isotopic compositions of sulfides indicate that reduced sulfur was mainly derived from the host rocks. Lead isotopic compositions of sulfides (206Pb/204=17.999~18.569, Pb207Pb/204Pb=15.673~15.764, and 208Pb/204Pb=38.083～39.126) indicate the metals were derived from the upper crust, possibly basement sedimentary rocks. 4. Zinc isotopic compositions of sphalerite vary each deposit in the region. The brown sphalerites hosted in Proterozoic and Cambrian carbonate have light zinc isotopes (δ66ZnIRMM=-0.406‰～-0.647‰, δ68ZnIRMM=-0.852‰～-1.284‰), whereas the yellow sphalerites hosted in Devonian to Permian carbonate enriched heavy zinc isotopes (δ66ZnIRMM=-0.347‰～-0.242‰, δ68ZnIRMM=-0.500‰～-0.684‰). Variation of zinc isotopes is controlled by trace elements such as Fe and Cu in sphalerite, and temperature of ore fluids.5. We proposed a model in which the metamorphic ore fluids were generated by metamorphism of deep sedimentary rocks during the Yanshanian orogeny along the Ziyun-Yadu fault and flowed along thrust faults in the basement, upward into structures in response to stress relaxation during the orogeny. Sulfides such as sphalerite and galena precipitated where the ore fluids mixed with reduced sulfur from the host rocks.