The size of functional nanocomplexes, which targets the brain tumor associated macrophages nanocomplex plays a very important role in their interaction with cells involving uptake, release and targeting selectivity. The size effects of nanocomplex on cell-based targeted delivery were studied to investigate if this phenomenon can be employed to combine the targeting peptide to provide a selective tumor associated macrophages targeted delivery system for anti-glioma therapy. Paclitaxel (PTX) was loaded into a core-shell structure of nanocomplex (PTX-Nanocomplex). Three different sizes of PTX-nanocomplex were prepared through nanoprecipitation. Rabies virus glycoprotein (RVG) peptide was conjugated to PTX-nanocomplex to form RVG-PTX-nanocomplex. Uptake, release, transportation and anti-glioma activities were studied in in vitro by using bone marrow derived macrophages (BMM) and tumor associated macrophages (TAMs), human glioma U87 cells, and neurons. The resulting RVG-PTX-nanocomplex had a spherical shape, with the size of 72 nm (small), 138 nm (medium), and 220 nm (large). The large-size RVG-PTX-nanocomplex showed greater uptake by BMM, but did not take by neurons. Co-cultivation of U87 and TAMs pre-loaded with largesize RVG-PTX-nanocomplexes provided significant anti-glioma activities. More importantly, large-size RVG-PTXnanocomplexes were selectively targeted to TAMs and effectively transported to U87 cells with lower side effects. We concluded that the large-size RVG-PTX-nanocomplex had promising potential uses in the TAMs targeted delivery system for glioma therapy.