Glioma is the most typical malignant brain tumor, and the chemotherapy to glioma is limited by poor permeability for crossing blood-brain-barrier (BBB) and insufficient availability. In this study, angiopep-2 modified lipid-coated mesoporous silica nanoparticle loading paclitaxel (ANG-LP-MSN-PTX) was developed to transport paclitaxel (PTX) across BBB mediated by low-density lipoprotein receptor-related protein 1 (LRP1), which is over-expressed on both BBB and glioma cells. ANG-LP-MSN-PTX was characterized with homogeneous hydrodynamic size, high drug loading capacity (11.08%) and a sustained release. In vitro experiments demonstrated that the targeting efficiency of PTX was enhanced by ANG-LP-MSN-PTX with higher penetration ability (10.74%) and causing more C6 cell apoptosis. ANG-LP-MSN-PTX (20.6%) revealed higher targeting efficiency compared with LP-MSN-PTX (10.6%) via blood and intracerebral microdialysis method in the pharmacokinetic study. The therapy of intracranial C6 glioma bearing rats was increasingly efficient, and ANG-LP-MSN-PTX could prolong the survival time of model rats. Taken together, ANG-LP-MSN-PTX might hold great promise as a targeting delivery system for glioma treatment.