The effects of administration of the immunomodulator Ergosan, an algal extract containing alginic acid, in juvenile rainbow trout (Oncorhynchus mykiss) exposed to AquaVac vaccination, were tested. Juveniles treated with Ergosan, 95 days after the beginning of first solid feeding and control fish fed solely on commercial diet, were vaccinated by immersion in AquaVac solution. The time-course of the effects of vaccination on liver immunorelated gene modulation and on the tolerance to stress manipulation connected with the vaccination was investigated. Liver and plasma sampling was performed at the following times: T=pre-vaccination, T0=5min, T1=2h, T2=8h, T3=24h, T4=48h and T5=72h post-vaccination. Interleukin-1beta (IL-1beta), interleukin-8 (IL-8), tumor necrosis factor alpha 2 (TNF alpha 2) and heat shock protein 70 (Hsp70) gene expression in trout liver was monitored by real-time PCR using Acidic Ribosomal Phosphoprotein P0 (ARP) as internal standard. The evaluation of the plasma cortisol levels was performed by EIA. In AquaVac-vaccinated fish, both the gene expression of Hsp70 and the plasma cortisol levels during the time-course were significantly (P<0.05) lower in Ergosan-treated fish with respect to control, indicating the positive role of Ergosan on handling stress tolerance. This study also demonstrated the stimulatory properties of Ergosan on cytokine genes expression involved in innate immune response: liver IL-1beta, IL-8 and TNF alpha 2 gene expression was significantly (P<0.05) higher in trout fed on Ergosan compared to control, indicating a positive role of this feed additive in improving the immune responsiveness to AquaVac vaccine.