Aim To investigate the relationship between the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) signaling pathway and cyclooxygenase-2 (COX-2) expression in THP-1 monocytes. Methods Human THP-1 monocyte was used as the research cell, and the time-dependent expressions of STAT3 phosphorylation and COX-2 were detected after IL-6 treatment for 0 to 48 hours. THP-1 monocytes were pretreated with 100 μmol/L S3I-201(an specific inhibitor of STAT3 signaling) for 24 hours and then treated with 10 μg/L IL-6 for certain time. THP-1 monocytes were divided into 4 groups:control group, S3I-201 group, IL-6 group and IL-6＋S3I-201 group, then the changes of STAT3 phosphorylation and COX-2 expression were detected. COX-2 mRNA expression was detected by real-time fluorescence quantitative PCR. The levels of STAT3 phosphorylation and COX-2 protein expression were determinated by Western blot. Results IL-6 could obviously induce STAT3 phosphorylation and COX-2 expression via a time-dependent manner in THP-1 monocytes. Phosphorylation level of STAT3 increased after IL-6 stimulation for only 5 minutes (P＜0.001), meanwhile, COX-2 mRNA and protein expressions was significantly upregulated, reaching peak at 1 h and 2 h respectively (P＜0.001). Compared with control group, COX-2 mRNA and protein expressions were both markedly suppressed in S3I-201 group (P＜0.01). Compared with IL-6 group, phosphorylated STAT3 level was downregulated in IL-6＋S3I-201 group (P＜0.001), and COX-2 mRNA expression was also decreased (P＜0.001), with COX-2 protein expression clearly suppressed (P＜0.05). Conclusion IL-6 is capable of activating the STAT3 pathway in THP-1 monocytes, which may play a role in COX-2 expression and further affect the process of atherosclerotic disease.