Eudiplozoon nipponicum is a sanguivorous monogenean of East Asian origin which parasitizes the gills of the common carp, Cyprinus carpio. One of the mechanisms which enable successful parasitic lifestyle is the utilization of compounds contained in excretory-secretory products of the parasite for possible modulation of the host physiological processes. We identified cysteine peptidase inhibitor (type I cystatin, also known as stefin) among the molecules secreted by E. nipponicum. These inhibitory molecules are generally known as regulators of endogenous processes related to the protein degradation. Besides, they can affect the blood digestion, immunomodulation of the host and the repair of its tissue damaged by the parasite. Our study aims to reveal the immunomodulatory potential of the stefin of E. nipponicum. During in vitro assays we used recombinant stefin which is capable of inhibiting cathepsin B and L as well as legumain. Using qPCR method we characterized the changes in the expression of cytokines by immune cells stimulated by LPS. Recombinant stefin of E. nipponicum caused significant downregulation of selected cytokines (IL-1beta, IL-8, TNF-alpha, IL-6 and IL-10) by porcine alveolar macrophages and monocyte derived macrophages. Our finding indicates possible role of this inhibitor in immunomodulation of the host, i.e., the infiltration of neutrophils, suppression of inflammatory response and differentiation of T cells. Luminol-enhanced chemiluminescence assays did not prove any significant effect of stefin on the activation of complement in carp’s plasma or oxidative burst in full blood.