Inflammation is related to cancer progression and many diseases. NSAIDs (non-steroidal anti-inflammatory drugs) are the most common medications for the treatment of anti-inflammatory function. These drugs that bind to enzymes such as COX-1 and COX-2 can be used as inflammatory biomarkers. Herein Gd-DO3A-Dif and Gd-DO3A-Fen were synthesized from DO3A conjugated to carboxylic acid derivatives of NSAIDs which were diflunisal and fenbufen. In this study, we expect that these gadolinium complexes conjugated with NSAIDs will potentially be able to target inflamed tissues in MRI. Scheme 1 shows the synthesis of Gd-DO3A-Dif and Gd-DO3A-Fen. Relaxivities of these complexes are slightly higher those of Gadovist® as shown table 1. The kinetic stability of these gadolinium complexes was comparable with Dotarem® employing the same type of macrocyclic chelate (Figure 1). In vivo MR experiment, inflamed tissue of left thigh exhibits strong enhancement more than 2 hours demonstrating inflammation targeting ability (Figure 2). Additionally, developed Gd-DO3A-Dif and Gd-DO3A-Fen inhibit COX-2 enzymes in immunofluorescence image confirming inflammation targeting properties of these complexes (Figure 3). In conclusion, we have synthesized gadolinium based MRI contrast agents for inflammation targeting by conjugating NSAIDs to DO3A-based ligand. Anti-inflammatory activities vary depending on the type of conjugated NSAIDs and the structure of the complexes.