The aim of this study was to investigate the role of p38 mitogen-activated protein kinase (MAPK) in cell migration induced by platelet-derived growth factor (PDGF). Western blot was performed to detect the phosphorylation of p38 in NIH3T3 cells treated with PDGF. A Transwell cell migration system was used to determine the effects of PDGF treatment on the migration of NIH3T3 cells and the influence of p38 deficiency on this process in a p38 gene knockout (p38(-/-)) mouse embryonic fibroblast cell line. On the stimulation of PDGF, the migration of NIH3T3 cells was significantly increased (P < 0.001) compared to the control and p38 MAP kinase was simultaneously phosphorylated. Furthermore, the PDGF-induced cell migration was significantly blocked in p38 gene knockout (p38(-/-)) mouse embryonic fibroblasts (MEFs) (P < 0.001) as compared with the wild type cells (p38(+/+)). p38 MAPK plays an important role in the regulation of cell migration induced by PDGF.