Angiopoietins are endothelial growth factors, which play crucial roles in normal vascular development and tumor angiogenesis. We examined the expression profiles of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), and Tie-2, a receptor for Ang-1 and Ang-2, in both colorectal adenocarcinoma and adjacent normal tissues, as judged by histology, in order to elucidate their relationships with microvascular density (MVD) and clinicopathologic properties. Higher MVD was associated with a lower degree of differentiation of colorectal adenocarcinoma. Immunohistochemical analysis revealed that the expression of Ang-2 and VEGF was significantly increased in colorectal adenocarcinoma compared to adjacent normal tissues (p < 0.01), and the expression of Ang-2 positively correlated with that of VEGF (r = 0.997, p < 0.01). In contrast, the expression of Ang-1 was lower in adenocarcinoma tissues than in adjacent normal tissues (p < 0.01), while there was no significant difference in Tie-2 expression in both tissues. Moreover, MVD was increased in Ang-2- and VEGF-expressing adenocarcinoma tissues compared to the Ang-2- and VEGF-negative tissues, respectively (p < 0.01). Importantly, MVD was lower in Ang-1-expressing adenocarcinoma tissues relative to Ang-1-negative tissues (p < 0.01). Furthermore, expression of Ang-2 as well as VEGF was significantly up-regulated in colorectal adenocarcinoma with diameters > or = 5 cm or with lymph-node metastases (p < 0.01). In conclusion, the increased expression of Ang-2 and the decreased expression of Ang-1 may be responsible for blood vessel formation and rapid growth of the colorectal adenocarcinoma.