The Sichuan-Yunnan-Guizhou (SYG) Pb-Zn metallogenic province is one of the most productive areas of Pb-Zn resources in China. The Fule deposit occurs in Permian carbonate and contains Pb-Zn reserves exceeding 1 Mt. To investigate the sulphur source, in situ S isotopic analysis of sphalerite and pyrite was carried out using nanoscale secondary-ion mass spectrometry. The results show that the delta S-34 values of the sulphide minerals range from +16.1 parts per thousand to +23.0 parts per thousand, higher than that of marine sulphates hosted in Permian carbonate rocks (+11 parts per thousand), but similar to that of sulphates over a broader area (+12.9 parts per thousand to +25.9 parts per thousand). The sulphates in the regional rocks could therefore represent an important source of S for the Fule deposit via thermochemical sulphate reduction. The S source of the Fule deposit is different from those of most other Pb-Zn deposits in the SYG Pb-Zn mineralization province, which were mainly derived from the ore-bearing strata. The delta S-34 values of the early to late generations and some single sulphide crystals from the cores to rims show a slight increasing trend, implying that partial Rayleigh fractionation took place in the Fule deposit. It is suggested that the Fule sulphide precipitation resulted from the mixing of a metalliferous fluid with a H2S-rich fluid derived from the regional strata. Combining the geology, mineralogy and S isotope results with previous Pb isotope studies, it is suggested that the Fule deposit should be attributed to a Mississippi Valley type deposit.