Abstract: Objective To investigate the role of COX-2 in acetaminophen-induced liver injury in rats. Methods Total of 40 male SD rats were randomly divided into 4 groups: control group, celecoxib treated group (group A), acetaminophen treated group (group B), and acetaminophen combined with celecoxib  treated group (group C). Each group was comprised of 10  rats and each rat was given a single dose of appropriate drug. After 24 hours, blood was collected to perform a serum biochemical test of liver  function, and liver tissue was harvested for pathological examination and COX-2 expression. Results There was obvious liver damage in group B, and liver injury of group C was aggravated by COX-2  inhibition than group B. There was no expression of COX-2 in hepatic tissue in control group. Positive COX-2 expression were observed in 7 rats of group B, with the rate of 70.0% and only one rat in group C, with the rate of 11.1%. Conclusions Intensity of COX-2 expression increased in group B and liver damage were aggravated after COX-2 blocking-up in the presence of COX-2-selective inhibitors. Induction of COX-2 expression may be a protective mechanism against acute liver injury induced by acetaminophen.