Abstract: Cyclooxygenase-2, which is a highly expressed protease in inflammation and tumor tissues, can serve as a monitor target for molecular imaging of inflammation and tumor. In this paper, a COX-2 targeted near-infrared probe (CMP) was synthesized based on a COX-2 small molecule inhibitor (celecoxib) and a water-soluble near-infrared dye (ICG-Der-02, MPA).The binding ability of COX-2 protein was verified by molecular docking, dynamic simulation and protein inhibition experiments. Results show that, at the cellular level, CMP can selectively accumulate at the cytoplasm of COX-2-positive cells. In vivo assays, probe guided-imaging in inflamed or cancerous tissues confirms that CMP can bind to the locally endogenic COX-2 and exhibit intense fluorescence. Importantly, the targeting specificity of CMP has been proved as the fluorescence can be significantly reduced by blocking COX-2 active site through preinjection with celecoxib. Therefore, the probe CMP, which possesses excellent near-infrared optical imaging capability and deep tissue penetration, and can specifically target to the high COX-2 site of inflammation and liver tumor, has the application prospect in inflammation and tumor monitoring.