© 2015 Elsevier B.V.. The East Kunlun Orogen in the Northern Qinghai-Tibet Plateau is an ideal region to investigate the geodynamic processes of magmatism related to the closure of the Paleo-Tethys Ocean. Here, we report petrology, zircon U-Pb geochronology, whole-rock geochemistry and multiple isotope data from granodiorites and the associated dioritic enclaves in a dominant Nan'getan granitoid in the East Kunlun Orogen. Zircon U-Pb ages indicate that the host granodiorites and dioritic enclaves were synchronously emplaced at ~243Ma. The granodiorites are medium- to high-K calc-alkaline, metaluminous (A/CNK=0.93-0.98), with high Al2O3 content (15.28%-16.10%), Mg# (47-49), very low Sr/Y ratios (127-217), high abundances of incompatible elements (Y=3.87-8.36ppm, Nb=3.04-5.71ppm, Th=3.04-5.71ppm), low (87Sr/86Sr)i (0.7050-0.7079), negative whole-rock εNd(t) (-8.2 to -5.8), (206Pb/204Pb) 243Ma of 18.520 to 18.772, (207Pb/204Pb) 243Ma of 15.611 to 15.650, (208Pb/204Pb) 243Ma of 38.227 to 38.528, δ18OSMOW=6.8‰-9.1‰, εHf(t) of -1.2 to +2.4. The dioritic enclaves (SiO2=51.08%-56.29%) have Mg# values of 48-51, with negative Eu anomalies (δEu=0.59-0.79), low (87Sr/86Sr)i (0.7058-0.7080), negative whole-rock εNd(t) (-8.2 to -5.8), (206Pb/204Pb) 243Ma of 18.376 to 18.809, (207Pb/204Pb)243Ma of 15.606 to 15.661, (208Pb/204Pb)243Ma of 38.244 to 38.540, δ18OSMOW=5.6‰-10.0‰, εHf(t) of -3.5 to +1.7. These isotopic features of arc-type rocks from the East Kunlun suggest that the parental magmas of the Nan'getan granodiorites and the dioritic enclaves originated from an enriched lithospheric mantle. The Nan'getan granitoids might have recorded the northward subduction of the Paleo-Tethys ocean lithosphere following the initial collision of the Bayan Har-Songpan Ganzi-East Kunlun terrane and the closure of the Paleo-Tethys Ocean at ~243Ma.