To examine paleodiets and habitats of extinct taxa and to understand long-term regional climate change, we determined the carbon and oxygen isotopic compositions of fossil herbivore teeth and soil samples from six localities in Yunnan Province, Southwest China, ranging in age from ∼10 Ma to the present. Although limited in spatial and temporal coverage, these initial results reveal significant changes in the environments and diets of mammalian taxa over the last 10 million years. Prior to 2–3 Ma, while most mammals examined had pure or nearly pure C 3 diets, some individuals consumed a small amount of C 4 grasses (up to 20% C 4). Since then, C 4 grasses became a significant dietary component for most herbivores as indicated by higher enamel-δ 13C values in the Pleistocene Yuanmou Formation and at Shangri-La, most likely reflecting an increased C 4 biomass in the region. The carbon isotope results show that the diets of mammals of ∼2.5–1.75 Ma from Shangri-La ranged from pure C 3 to pure C 4 while 1.7 Ma horses from Yuanmou had 0–70% C 4 grasses in their diets. Mammals living at ∼8–7 Ma in the Yuanmou and Lufeng region had very similar diets and habitats, with similar climatic conditions. Increased C 4 biomass after ∼3–4 Ma suggests a significant change in certain aspects of regional climate, such as increased seasonality of rainfall or an increase in seasonal drought and fires as these factors are important to modern grasslands. The data also show that unlike the Siwalik fauna in the Indian subcontinent, mammals in Yunnan on the southeast side of the Himalayan–Tibetan Plateau lived in an environment dominated by dense forests until ∼3–4 Ma. Nonetheless, both δ 13C values of paleosol carbonates and fossil enamels indicate that C 4 grasses were present in the Yuanmou region in the latest Miocene and Pliocene (∼8–3.5 Ma), likely in greatly dispersed, small patches of open habitats where the forest canopy was broken or on flood plains, and the C 4 biomass increased significantly after ∼3.5 Ma. The oxygen isotope results from Yuanmou (Xiaohe Formation) show a positive shift after ∼8.5 Ma, which is similar in timing and magnitude to δ 18O shifts observed in horses and rhinos from the Linxia Basin and in fossils and paleosols from Pakistan and Nepal, suggesting a shift toward a drier climate at the northeast, southeast, and southern borders of the Tibetan Plateau during the late Miocene. Taken together, the carbon and oxygen isotope data indicate a general drying of the local climate over time and a change from a largely dense-forest environment at ∼8 Ma to a more open environment with a mosaic of forests and grasslands after 3–4 Ma in the Yuanmou region. Intra-tooth δ 13C and δ 18O variations within individual fossil teeth from Yuanmou suggest a stronger seasonality of rainfall at ∼1.7 Ma than in the late Miocene. The spatial and temporal δ 13C and δ 18O variations observed in mammalian teeth from Yunnan likely reflect changes in regional climate and/or tectonics, but more data are needed to fully explore the significance of the regional patterns in the δ 18O and δ 13C data in relation to climate and tectonic evolution of the region.