Abstract: Objective To evaluate the efficacy of nonsteroidal anti-inflammatory drug indomethacin on tumor growth and microvessel angiogenesis of human colon cancer xenografts in nude mice. Methods Human colorectal cancer HCT116 cells were inoculated subcutaneously into BALB/c-nu/nu mice. After daily treatment with oral indomethacin for 4 weeks (3 mg·kg^-1·d^-1), the mice were sacrificed by cervical dislocation, and immunohistochemical staining was employed to determine microvessel density (MVD) and expression of vascular endothelial growth factors (VEGF) in the tumor tissues. Results Growth of HCT116 tumor was significantly suppressed by indomethacin. The tumor volume (mm³) was 458.89±32.07 in the treated group versus 828.21±31.59 in the control group (P<0.05). The MVDs of the treated and control groups were 19.50±5.32 and 37.40±4.93 respectively (P<0.001), and VEGF expressions were 1.19±0.17 and 1.90±0.48 (P<0.01), respectively. MVD and VEGF expression in the treated tumor tissue declined noticeably as compared with the controls. There was a positive correlation between the decrease of VEGF expression and that of MVD (r_s=0.714, P<0.05). No obvious toxicity was observed in nude mice. Conclusion Indomethacin can inhibit the growth of transplanted human colorectal HCT116 tumor in association with a significant reduction in angiogenesis, which may be achieved through inhibition of VEGF.