Vascular endothelial growth factor (VEGF) is a potent angiogenic and vascular permeability factor. Recent studies have shown that the VEGF levels increase in several cell types, for example, macrophages and smooth muscle cells after LPS stimulation, suggesting that it is important in the initiation and development of sepsis. In particular, LPS-regulated contractility in lung pericytes may play an important role in mediating pulmonary microvascular fluid hemodynamics during sepsis. This study investigated the production of VEGF by rat lung pericytes in response to LPS. LPS was found to enhance VEGF mRNA expression in a concentration-dependent manner peaking 2 h after stimulation in pericytes. Vascular endothelial growth factor protein levels in conditioned medium and in cell lysate also increased on increasing LPS and peaked after 24 to 48 h. LPS also significantly augmented iNOS expression in lung pericytes within 6 h. However, iNOS mRNA induction occurred later than LPS-induced VEGF mRNA increases. Interestingly, attempted inhibition with nuclear factor-kappaB or tyrosine kinase did not suppress LPS-induced augmented VEGF mRNA expression in lung pericytes, although both inhibitors markedly inhibited LPS-induced iNOS mRNA expression. SB203580, a p38 MAP kinase inhibitor, repressed LPS-induced VEGF mRNA expression. Furthermore, LPS stimulated a rapid and sustained phosphorylation of p38 MAP kinase. These results show that pericytes produce VEGF in response to LPS stimulation, and that this may be partly mediated by the p38 MAP kinase pathway. More research should be done to establish the regulation of capillary hemodynamics and identify mechanisms of their regulation.