Abstract: Objective To investigate the influence of multi-target inhibitor vandetanib combined cytotoxic drugs carmustine (BCNU) on the proliferation and invasion of rat glioma cell C6. Methods The MTT assay was used to test the impact of drugs on cell viability and changes of cell morphology were observed by HE staining. Rat glioma cell C6 model was established by situ injection, and six days later they were divided into the vandetanib group 50 mg/(kg·d), BCNU group 25 mg/(kg·d), the combination group (vandetanib+ BCNU) and the control group. Dose the rats 7 times every other day for 2 weeks, then take the rats' brain after the decapitation, section the tumor tissues and calculate the volume of the tumor. Immunohistochemical SP assay was used to mark tumor vascular endothelial cells, and detect the microvessel density (MVD) in transplanted tumors and the expression of MMP1 protein related to tumor invasiveness. Apoptotic index was tested by TUNEL technique. Results The combination group was much remarkable to promote the apoptosis than that of the BCNU group (P <0.01). Compared with the control group, tumor volumes of the BCNU group decreased by (P<0.05) The expression of MMP1 in xenografts was weak positive(++), and there was no significant change in MVD，but the apoptosis rate of transplanted tumor cells was 62.6%(P<0.05). Tumor volume of the combination group wasdecreased about 56% and the expression of MMP1 was negative(+), and MVD decreased by 53%(P <0.05). Conclusion The combination therapy can not only significantly inhibit the growth of glioma cell C6, but also decrease the expression of MMP1 related to neoplasm invasiveness. Therefore, it provides experimental basis for the joint multi-target inhibitors and cytotoxic drugs in clinical treatment of malignant glioma.