Multiple long non-coding RNAs (lncRNAs) have been demonstrated to be involved in liver disease. Increased cyclooxygenase-2 (COX-2) levels have also been reported to be involved in the progression of liver cirrhosis. In the present study, the correlations between lncRNA-COX-2 RNA expression levels, COX-2 mRNA expression levels and liver fibrosis were examined. Liver fibrosis was induced by intraperitoneal injection of carbon tetrachloride (CCl4) in mice for 2months (CCl4-2M) or 3months (CCl4-3M). Liver histopathological evaluation was conducted using hematoxylin and eosin and Masson trichrome staining. Hepatic expression of COX-2 and lncRNA-COX-2 was evaluated by reverse transcriptionquan-titative polymerase chain reaction and immunohistochemical staining. Compared with the control group, fibrotic areas were increased four and nine times in the CCl4-2M group and the CCl4-3M group, respectively. LncRNA-COX-2 and COX-2 upregulation were observed in the cirrhotic liver. COX-2 mRNA expression levels and lncRNA-COX-2 RNA expression levels were significantly positively correlated with the fibrotic area. In addition, COX-2 mRNA expression was significantly positively correlated with lncRNA-COX-2 expression. These results suggest that expression of COX-2 and lncRNA-COX-2 increased with the progression of liver fibrosis. LncRNA-COX-2 may potentially be considered as a novel therapeutic target for liver fibrosis.