Background: In this paper, the evaluation of the antiviral effect of a Mexican propolis on Pseudo Rabies Virus (PRV) was performed by infecting cell cultures of MDBK. Materials and Methods: First, the level of cytotoxicity of the ethanol extract of propolis (EEP) was determined, subsequently, infective dose of PRV strain Shope was determined and finally, we performed the interaction of the virus with EEP (two hours before, during and two hours after infection) in MDBK cells. Also, in order to determine the possible effects of propolis on the virus, cell culture samples subjected to the different treatments mentioned above were processed for Transmission Electron Microscopy (TEM). Also, cell culture samples with the same treatments were processed for Transmission Electron Microscopy (TEM) to observe possible alterations of propolis on the virus. Results: It was determined that administration of 0.5 mg / ml of EEP two hours before infection caused a reduction in the number of plaque forming units compared to the rest of the treatments used or with the infected and untreated culture, it is important to note that the difference found was statistically significant (p <0.01). By other hand, viral particles with altered morphology were observed at MET suggesting a possible damage to the viral envelope proteins. We also found virions in an electro-dense layer formed around the cell membrane. This seems to affect the penetration of the virus and its replication cycle. Conclusion: This study demonstrated the antiviral activity of EEP used and its results open perspectives to explore the possibility of using propolis as a preventive method against pseudo rabies.