BACKGROUND: Antimicrobial agents can alter physiological status and immunity system of the host, and use of hematological indices are the appropriate marker for monitoring them. OBJECTIVES: The present study intended assessment of changed hematological indices of rainbow trout challenged with streptococcosis/lactococcosis agents following oral administration of florfenicol. METHODS: The purchased fish (55±7.5 g) were examined through a randomized blocks design in the replicated 6 treatments consisting of without/with the infectious challenge of each pathogen separately and without/with medicated feeding in 15 mg/kg-1 BW for 10 consecutive days. Doses of Streptococcus iniae (2.87×107 CFU/ml) and Lactococcus garvieae (6.8×105 CFU/ml) equal to 30% of LD50 values were applied in the main experiment. At the end of trial, blood was sampled via caudal vein. Measurement of hematocrit and hemoglobin has been accomplished according to standard methods, and the number of blood cells was counted by hematocytometer. RESULTS: Findings pointed out PVC%, Hb value and RBCs count of groups that received the drug were reduced significantly than control (p < /em><0.05). 10-day administration of flornfeicol in the mentioned dosage could cut down lymphocytes statistically (p < /em><0.05). On the other hand, monocytes, neutrophils, and other blood cells were enhanced following administration of therapeutical dosage (p < /em><0.05). CONCLUSIONS: It seems that oral consumption of florfenicol could improve innate immunity, especially through enhancement of hematocytes. However, due to reduced frequency of blood lymphocytes, and as the problem of anemia in fish following drug consumption is still observed, it is recommended that in case of reduction of losses and improvement of clinical symptoms, the lowest FDA-suggested levels of the antibiotic for treatment should be used.