Gold nanoparticles are ideal probes for studying intracellular environments and energy transfer mechanisms due to their plasmonic properties. Plasmon resonance energy transfer (PRET) relies on a plasmonic nanoparticle to donate energy to a nearby resonant acceptor molecule, a process which can be observed due to the plasmonic quenching of the donor nanoparticle. In this study, a gold nanosphere was used as the plasmonic donor, while the metalloprotein cytochrome c was used as the acceptor molecule. Differential interference contrast (DIC) microscopy allows for simultaneous monitoring of complex environments and noble metal nanoparticles in real time. Using DIC and specially designed microfluidic channels, we were able to monitor PRET at the single gold particle level and observe the reversibility of PRET upon the introduction of phosphate-buffered saline to the channel. In an additional experiment, single gold particles were internalized by HeLa cells and were subsequently observed undergoing PRET as the cell hosts underwent morphological changes brought about by ethanol-induced apoptosis.