Despite advances in cancer therapy, effective local treatment remains a formidable challenge due to the limit of efficient drug delivery method and the toxicity of chemotherapeutics. In the current study, a combined system was developed for simultaneous delivering doxorubicin (DOX) and cis-platinum (CDDP) to the lungs via pulmonary administration. Methoxy poly(ethylene glycol)-poly(ethylenimine)-poly(l-glutamate) (mPEG-OEI-PLG) copolymers were synthesized as a carrier for the co-delivery of DOX and CDDP. The co-delivery nanoparticles (Co-NPs) were formed with mPEG-OEI-PLG via electrostatic interactions for DOX loading and chelate interactions for CDDP loading, respectively. The results of in vitro cytotoxicity assays against B16F10 cell line showed that Co-NPs exhibited higher cytotoxicity than those treated with either DOX or CDDP alone. In the B16F10 tumor-bearing mice models, local delivery of Co-NPs by pulmonary administration demonstrated that Co-NPs had highly efficient accumulation in the lungs, especially in the tumor tissues of the lungs, but rarely in normal lung tissues. Moreover, Co-NPs exhibited higher anti-tumor efficiency for metastatic lung cancer than that in the single treatment of DOX or CDDP, while no obvious side effects were observed during the pulmonary treatment. The present pulmonary delivery by exploiting co-loaded nanoparticles was proved to be a promising drug delivery strategy for effective lung cancer therapy.