NF-kappa B is a critical transcription factor that plays an important role in mediating inflammation, the immune response, and cell proliferation. The activation of NF-kappa B leads to an enhancement of proinflammatory mediator expression, which is implicated in the pathogenesis of a variety of diseases. Therefore, methods that allow the intracellular tracking of NF-kappa B are particularly attractive because they can provide information regarding the pathways or stimulation responses that are involved in the activation of NF-kappa B. In this work, we report a novel platform to track intracellular NF-kappa B by employing the conjugated iridium(III) complex 1, which was synthesized through the unique combination of a luminescent iridium(III) moiety with the natural product oridonin. Experiments conducted with p50 knockdown cells revealed that complex 1 could detect the p50 subunit of NF-kappa B in cellulo. Furthermore, complex 1 tracked NF-kappa B translocation induced by tumor necrosis factor-alpha (TNF-alpha) as a model stimulus, without affecting the translocation process itself. To the best of our knowledge, complex 1 is the first metal-based compound that has been reported to be capable of monitoring intracellular NF-kappa B in living cells.