Caffeic acid phenethyl ester (CAPE), a component of honeybee propolis, has been reported to hold various biochemical responses. In the preliminary study, we found that CAPE inhibited the growth of C6 glioma cells in a dose dependent and time dependent manner as shown by the results of trypan blue dye exclusion assay and cell proliferation assay. In addition, the cell number percentage of the G0/G1 phase increased to 85% after the treatment with 50 microM of CAPE for 24h. After treatment with CAPE (50 microM) for 6h, it demonstrated that the protein level of hyperphosphorylated pRb decreased, and cyclin dependent kinase inhibitors p21, p27, and p16 were marked up-regulated. The association of CDK2 and cyclin E that affects the CDK2 activity decreased. When C6 cells were grown as xenografts in nude mice, treatment with CAPE (1-10mg/kg; ip) induced a significant dose dependent decrease in tumor growth by evaluating tumor volume and tumor weight. Histochemical and immunohistochemical analysis revealed that CAPE treatment significantly reduced the number of mitotic cells and proliferating cell nuclear antigen (PCNA)-positive cells in C6 glioma. These results suggest that CAPE presents an antitumor potential for glioma by inhibiting the growth of tumor cells.