Background: Gene Electro Transfer (GET) is a promising method for therapeutic purposes. Intratumoral GET has reached clinical evaluation for antitumor treatment. An increasing number of studies suggests that antitumor effectiveness not only depends on the transfection efficiency, but also on the induction of immune responses and vascular effects that result in the nonspecific induction of cell death. Real time noninvasive optical imaging methods allow longitudinal studies of these dynamic biological processes. Objective: In the present study, a noninvasive bioluminescence technology was used to further explore the phenomena associated with GET to tumors by a real time monitoring of the transfection efficiency as well as cell death following the treatment. Method: By using transgenic light-producing tumors, tumor growth was visualized, and since dead cells stop producing light, effectiveness of the treatment or the emergence of necrotic areas in the tumors was followed visually. The transfection efficiency of reporter genes (iRFP protein and luciferase) in the subcutaneous tumors was also evaluated. Results: Our results showed that the GET of a reporter gene can lead to nonspecific antitumor effectiveness and even complete regression of tumors. Using light-producing tumors, we were also able to indirectly visualize the previously described vascular effects of electroporation. Additionally, using the intratumoral GET of a luciferase encoding plasmid, we localized the source of the expression mainly in the peritumoral and not in the tumoral region. Conclusion: The data obtained provide new insights into some of the phenomena associated with GET to tumors, which should be taken into account when designing improved and more effective cancer gene therapy, in order to accelerate the transfer of the technology into clinical trials.