Oxytetracycline (OTC) and florfenicol (FF) are antibiotics with high potency against the bacterial diseases. Therefore, they are commonly used against bacterial infection in fish farming. The present work aimed to study the effect of different doses of oxytetracycline (0, 40, 80, 120mg/kg basal diet) and florfenicol (0, 7.5 , 15 , 22.5 mg/kg basal diet) on chromosomal structure and micronuclei induction in RBCs of Nile tilapia fish. The results revealed that the dose of 40 mg OTC/kg basal diet and the dose of 7.5 mg FF/kg basal diet showed non-significant increases in chromosomal aberrations compared with control. The same dose of florfenicol caused significance difference in the frequency of micronuclei compared with control group. The other doses of OTC and FF were significant increases (p<0.05) in total chromosomal aberrations (11.40 & 15.60 and 16.80 & 19, respectively) and the frequency of micronuclei (5.4 & 6.8 and 6.4 & 8.5, respectively) compared with control group (8 and 2.4, respectively). The mutagenic influence of therapeutic and super- therapeutic doses of FF treatment was more obvious on chromosomal structure and micronuclei frequency compared to therapeutic and super-therapeutic doses of OTC treatment. These findings, in general, add to the fact that fish such as tilapia ( Oreochromis niloticus ) is a promising models in vivo for monitoring the mutagenic effect of substances on aquatic ecosystems