The aim of the present study was to investigate the effect of probioenzyme on the control of yersiniosis as well as to assess the impact of probioenzyme on the expression of immune-related genes in the head kidney of rainbow trout (Oncorhynchus mykiss). Probioenzyme was supplemented at 0.3, and 0.5g/kg diet and fed to fish (average weight: 26 g) in 200l tanks for 60 days. At the end of the feeding period, fish were challenged  with yersinia ruckeri. Only the fish fed the diet containing high dose of probioenzyme showed significantly (p<0.05) improved  protection against y. ruckeri compared to the low dose and control groups. Subsequently, real-time PCR was employed to determine the mRNA levels of IL-1β and TNF- α cytokines in the head kidney of the control and probioenzyme groups. High dose of probioenzyme significantly (p<0.05) up-regulated the TNF- α transcription in the kidney compared with low dose and control groups. Meanwhile, the probioenzyme didn,t change nterleukin-1β mRNA level in the kidney in treatment groups compared with control group (p>0.05). Only, high dose of  probioenzyme noticeably differs IL-1β and TNF-α gene expressions. Based on results, expression levels of studied cytokines were different, dose-dependent and tissue-specific. Results showed that cytokine gene expressions, especially TNF-α, in kidney may affect fish disease resistance. Present study suggests that probioenzyme especially at 0.5g/kg feed may effectively stimulate the immune system and enhance disease resistance in rainbow trout. Meanwhile, it is necessary to  study effects of probioenzyme on cytokines in various tissue and different growth period of breeding species.