Background. Transplanted cells need a microenvironment for proliferation and neovascularization. As an important component of the microenvironment, fibroblasts play a role in the process of tumor growth. With that in mind, we planned to activate fibroblasts in vitro and investigate the expression of cyclooxygenase-2 (COX-2) and hepatocyte growth factor (HGF) which can promote the proliferation and neovascularization of the transplanted liver cells. Methods. Fibroblasts were isolated from 20-day-old fetal Sprague-Dawley rats and incubated in the absence or presence of rat hepatoma CBRH-7919 cell supernate. On days 1, 2, 3, 5, and 7 the incubated fibroblasts were taken for detection of the levels of HGF and COX-2 by immunocytochemistry and the levels of HGF mRNA and COX-2 mRNA by reverse-transcription polymerase chain reaction. Results. When incubated in the presence of CBRH-7919 cell supernate, the fibroblasts could be activated to myofibroblasts that expressed alpha-smooth muscle actin at a high level, and the fibroblasts expressed COX-2, COX-2 mRNA, HGF, and HGF mRNA at higher levels, reaching a peak on day 3 and maintained at high levels until on day 7. Conclusions. Fibroblasts can be activated by CBRH-7919 cell supernate. Activated fibroblasts can express COX-2 and HGF at higher levels. Maybe we can take advantage of the activated fibroblasts to promote the neovascularization and proliferation of transplanted liver cells.