The present study is performed to compare the electrophilic substitution radioiodination reaction of two non-steroidal anti-inflammatory drugs namely, Piroxicam (Pirox) and Meloxicam (Melox) with 125I where both chloramine-T (CAT) and iodogen were used as oxidizing agents. The factors affecting the percent of radiochemical yields such as drug concentration, pH of the reaction mixtures, different oxidizing agents, reaction time, temperature and different organic media were studied to optimize the conditions for labeling of Pirox and Melox and to obtain high radiochemical yields. The maximum radiochemical yield of 125I-Piroxicam (125I-Pirox) was 94% using 3.7 MBq of Na125I, 0.4 mM of Pirox as substrate, 3.6 mM of chloramine-T (CAT) as oxidizing agent in acetone at neutral pH = 7 and at 60 °C within 20 min where the maximum radiochemical yield of 125I-Melox was 92% using 0.7 mM of Melox as substrate, 0.62 mM of iodogen as oxidizing agent in acetone at neutral pH = 7 and at 25 °C within 30 min. The radiochemical yields were determined by TLC and high-pressure liquid chromatography (HPLC). Tracers showed good localization in inflamed muscle either septic or sterile. The collected data indicates that Pirox and Melox can be used as antiinflammatory imaging agents at 24 and 2 h post injection, respectively.