Medicinal plants have been successfully used to enhance the growth and immunity of fish during recent decade. The experiments herein were designed to assess the dietary effects of oak acorn (Quercus brantii) extract (OAE) on blood parameters, serum and skin mucus immune responses and resistance antibacterial activities of rainbow trout (Oncorhynchus mykiss) skin mucus against Yersinia ruckeri and Streptococcus iniae. Four hundred and fifty fingerlings (10.45 ± 0.24 g) were randomly stocked in fifteen tanks and fed experimental diets containing 0 (control), 100 (OAE1), 200 (OAE2), 400 (OAE3) and 600 (OAE4) mg/kg of OAE for eight weeks. At the end of the experiment, neutrophils (NEU), white blood cells (WBC) and hematocrit (Ht) and haemoglobin (Hb) levels significantly increased in the dietary treatments compared to those of the control. Higher lysozyme (Lys) activities and agglutinations (Agglu) were found in OAE2, OAE3 and OAE4. The alternative complement activity (ACH50) increased in supplemental the level of total immunoglobulin (total Ig) and skin mucus protease was highest in OAE3. The lysozyme activity of skin mucus and alkaline phosphatase (ALP) was enhanced in the OAE2, OAE3 and OAE4 groups. In vitro antibacterial activity tests showed that skin mucus effectively kills Y.ruckeri and S.iniae. Our findings further revealed the beneficial effects of dietary OAE on innate and mucosal immune responses, as well as the antibacterial activity of skin mucus of rainbow trout fingerlings.