The Fule Pb-Zn deposit is located in the western margin of the Yangtze Block, South China. This deposit structurally occurs in the Mile-Shizong-Shuicheng regional fault and is an important part of the Sichuan-Yunnan-Guizhou (SYG) Pb-Zn metallogenic province. Ore body is buried and occurs along the interlayer tectonic belt as stratiform shape. Sulfide ore is hosted by the middle Permian Yangxin Formation dolostone. Ore minerals are mainly sphalerite, minor galena and pyrite, with rare chalcopyrite and tetrahedrite, and gangue minerals are dominantly calcite and dolomite. Sulfide ore has massive, veined or disseminated structures with granular (euhedral, subhedral and anhedral) and metasomatic relict textures. There are more than 5 million tones (Mt) of sulfide ore, grading >10% Zn + Pb, and can up to 60% Zn + Pb. This paper presents the detailed ore deposit geology, and C-O, S and Pb isotopic data, aiming to reveal the sources of mineralizing elements and ore genesis. Calcite has delta C-13 values ranging from 1. 25%o to 2.01 parts per thousand, mean 1.64 parts per thousand, which are similar to those of marine carbonate rocks, but are higher than those of mantle and sedimentary organic matters. However, 818 0 values of calcite range from 17.21 parts per thousand to 17.74 parts per thousand (mean 17.49 parts per thousand), which are lower than those of carbonate rocks and organic matters, but are higher than those of mantle. Such C-O isotopic data suggests that the source of C is carbonate wall rocks, and O isotope signatures are generated by water/rock interaction between fluids and carbonate rocks. delta S-34 values of sulfide minerals range from 10.04 parts per thousand to 16.43 parts per thousand (ay. 14. 12 parts per thousand), indicating a feature of heavy S isotopes-enriched and the sources of reduced S in the hydrothermal fluids are originated mainly from evaporites within sedimentary strata by thermal-chemical sulfate reduction (TSR). Single-grain galena has (206)pb/Pb-204, (207)pb/Pb-204 and Pb-208/Pb-204 ratios ranging from 18. 530 to 18. 610 (ay. 18. 564), 15. 694 to 15. 702 (ay. 15. 697) and 38. 569 to 38. 657 (ay. 38. 601), respectively. These Pb isotopic data overlap with those of ore-formation age-corrected country sedimentary rocks and basement metaphoric rocks. Such Pb isotopic signatures demonstrate that the main sources of metal Pb are sediments and basements. This study proposes that the Fule is a carbonate-hosted, anticline and interlayer structure-controlled, stratiform, epigenetic, dispersed elements-enriched and high grade Pb-Zn deposit that formed under the background of tectonic regime shifted from extension to compression and then to extension. All those metallogenic features are probable to be related to both the Emeishan mafic magmatism and Indosinian Orogeny.