The Cangyuan Pb-Zn-Ag polymetallic deposit is located in the Baoshan Block, southern Sanjiang Orogen. The orebodies are hosted in low-grade metamorphic rocks and skarn in contact with Cenozoic granitic rocks. Studies on fluid inclusions (FIs) of the deposit indicate that the ore-forming fluids are CO2-bearing, NaCl-H2O. The initial fluids evolved from high temperatures (462–498 C) and high salinities (54.5–58.4 wt% NaCl equiv) during the skarn stage into mesothermal (260–397 C) and low salinities (1.2–9.5 wt% NaCl equiv) during the sulfide stage. The oxygen and hydrogen isotopic compositions (d18OH2O: 2.7–8.8‰; dD: 82 to 120‰) suggest that the ore-forming fluids are mixture of magmatic fluids and meteoric water. Sulfur isotopic compositions of the sulfides yield d34S values of 2.3 to 3.2‰; lead isotopic compositions of ore sulfides are similar to those of granitic rocks, indicating that the sulfur and ore-metals are derived from the granitic magma. We propose that the Cangyuan Pb-Zn-Ag deposit formed from magmatic hydrothermal fluids. These Cenozoic deposits situated in the west of Lanping-Changdu Basin share many similarities with the Cangyuan in isotopic compositions, including the Laochang, Lanuoma and Jinman deposits. This reveals that the Cenozoic granites could have contributed to Pb-Zn-Cu mineralization in the Sanjiang region despite the abundance of Cenozoic Pb-Zn deposits in the region, such as the Jingding Pb-Zn deposit, that is thought to be of basin brine origin.