Whether or not an intrusive rock altered by hydrothermal fluid could give geologically meaningful isochron age is an important issue of geochronology. Oxygen and Rb-Sr isotopic compositions were analyzed for altered and unaltered minerals from the Yueshan quartz diorite in Anhui. The sample gave apparent oxygen isotopic temperature of 470 ± 15°C for quartz-hornblende (unaltered) pair, 340 ± 10°C for quartz-biotite (unaltered) pair and 265 ± 20°C for quartz-plagioclase (unaltered) pair. The relation of Oxygen isotopes from the unaltered minerals suggested a retrograded re-equilibrium among minerals during rock cooling. The Rb-Sr isochron of the three unaltered minerals (biotite, hornblende and plagioclase) gave an age of 137.6 ± 1.2 Ma (MSWD = 0.07), which agrees with the previous Ar-Ar date within analytical uncertainties. Comparing with quartz-unaltered apparent isotopic temperatures, the quartz-biotite (altered) temperature of 310 ± 10°C and the quartz-plagioclase (altered) temperature of 325 ± 25°C were significantly changed, suggesting that their oxygen isotopic systems were disturbed during alteration. However, unaltered and altered (totally 6) minerals gave a Rb-Sr isochron showing good linearity (MSWD = 0.81) and corresponding to an age of 136.81 ± 0.77 Ma, agreeing with the age given by the isochron constructed by the unaltered minerals. Meanwhile, Rb, Sr concentrations and Sr isotopic ratios of the altered biotite and plagioclase were changed because of alteration. However, the isochron age is not affected since the values of 87Rb/86Sr and 87Sr/86Sr of altered minerals moved along the isochron. This suggested an isotopic exchange between minerals and the internal fluid that was identical to the whole rock in the isotopic composition. The case studied suggested that Oxygen isotopic system could be disturbed while the Rb-Sr could still give a geologically meaningful age when the granite was affected by an internal fluid during the low temperature alteration.