The angiopoietin/Tie2 system is a predominant regulator of vascular development. This vascular development appears to be controlled and completed by the coordinated actions of two vascular cells, endothelial cells and their surrounding supporting cells, smooth muscle cells, or pericytes. The role of the angiopoietin/Tie2 system has been studied, but these studies are limited mostly to endothelial cells. In this study, using bovine retinal pericytes (BRP), we investigated the effect of two known angiogenic stimuli, hypoxia and vascular endothelial growth factor (VEGF) treatment, on the regulation of the angiopoietin/Tie2 system. Hypoxia (2% O(2) concentration) was acquired by a hypoxia chamber. Both hypoxia and VEGF (10 ng/ml) treatment significantly increased angiopoietin-1 (Ang1) mRNA expression. This marked augmentation occurred acutely (maximal increase at 2 h) and subsequently decreased. In contrast, angiopoietin-2 (Ang2) mRNA expression was unaltered in BRP upon both treatment. Significant up-regulation of Tie2 mRNA expression was found and lasted up to 12 h. However, using bovine aortic endothelial cells (BAEC), we found that only Ang2 expression, but neither Ang1 nor Tie2, responded to these two angiogenic stimuli, which was consistent with many previous reports. In conclusion, our data suggest that both hypoxia and VEGF treatment differentially regulate the angiopoietin/Tie2 system in the two vascular cells and that, particularly in BRP, the regulation of Ang1, but not Ang2, and Tie2 expression may play an important role in vascular development.