Nisin, a member of class I bacteriocins known as lantibiotics, is produced by the lactic acid bacterium Lactococcus lactis and is characterized by a wide spectrum of antibacterial activity against gram-positive bacteria. This characteristic in conjunction with its low toxicity and safety of use in food has contributed to the worldwide success of nisin as a natural food preservative. This lantibiotic has attracted interest as a potential natural therapeutic agent for the control of bacterial infections. However, similar to other antimicrobial peptides of natural origin, the spectrum of biological activity of nisin surpasses its antibacterial properties, encompassing interesting and incompletely understood immunotropic characteristics. This paper is a systematic review of the current information about the potential immunomodulatory properties of nisin based on in vitro and in vivo studies in various experimental models. We also discuss the effect of potentially probiotic, nisin-producing L. lactis strains on the immune system of animals. Copyright © 2020 Elsevier Inc. All rights reserved.