The present study investigated the effects of combination of dietary Bacillus subtilis and trans-cinnamic acid on serum biochemical parameters, innate immune responses and resistance of rainbow trout, Oncorhynchus mykiss to Yersinia ruckeri. Six experimental groups of fish with mean weights of 20.58 +/- 0.35 g were used in the study. Five experimental groups of fish were fed diets containing Bacillus subtilis (10(7) per gram) or a mix of the Bacillus subtilis (BS) and trans-cinnamic acid (25 mg/kg-25trcBS, 50 mg/kg-50trcBS, 75 mg/kg-75 trcBS, 150 mg/kg-150 trcBS), whereas an additive-free basal diet served as the control (Cont). In this study, an increase was observed in granulocyte percentage, respiratory burst activity, phagocytic activity, phagocytic index, myeloperoxidase activity and total antiprotease activity especially in fish fed with mix of the BS and trans-cinnamic acid-supplemented diets (p < .05). Moreover, at the end of the 20-day challenge period the survival rates and antibody titre (p < .05), and relative per cent survival were higher in the BS group and all trcBS groups compared with control group. As a conclusion, the results in the present study show that feeding rainbow trout with diets containing a mix of B. subtilis and trans-cinnamic acid over a 60-day period might be sufficient for improving fish immune responses and disease resistance against Y. ruckeri.