Inhibitors against cyclooxygenase-2 (COX-2), an inducible enzyme that catalyzes prostaglandin synthesis, are widely used in clinical. However, the potential hepatic toxicity of COX-2 inhibitors remains incompletely investigated. We report in this study that a clinically available COX-2 inhibitor, celecoxib, exacerbates porcine serum (PS)-induced hepatic fibrosis and induces hepatocellular necrosis in an experimental liver fibrosis model. Histological results revealed that although celecoxib by itself did not cause notable hepatic damages, it markedly enhanced hepatic fibrosis that had been initiated by PS. While PS alone did not cause any necrotic change in liver cells, the addition of celecoxib resulted in hepatocellular necrosis in PS-treated animals. Notably, celecoxib enhanced reduction of plasma prostaglandin E(2) (PGE(2)) levels induced by PS. Taken together, our results indicate that treatment with celecoxib may exacerbate liver fibrosis and cause hepatocellular necrosis. This may be associated with reduction in PGE(2) as an inheritance consequence of inhibition of COX-2.