Enrofloxacin, a fluoroquinolone and its interaction with monensin, an ionophore drug was studied to explore the relationship on the influence of enrofloxacin in the culmination of monensin toxicity in broiler chicken. Enrofloxacin (10mg/Kg BW, per os for 3 consecutive days) caused a significant decrease in aniline hydroxylase level on day 3 post-treatment and a reversal effect was noticed on day 6 post-treatment, indicating its reversible inhibitory effect on liver microsomal enzymes. Enrofloxacin when combined with monensin resulted in a significant increase in serum creatine kinase, aspartate aminotransferase and alanine aminotransferase levels relating to an injury on heart and liver which are target organs for monensin toxicity and there was a significant decrease in broilers performance. On day 3 post treatment histology of heart and liver revealed degenerative changes with multifocal infiltration of mononuclear cells. However the trends in histological changes were found to tend towards normal on day 6 post treatment. Co-administration of enrofloxacin and monensin even at the recommended level could result in toxic interactions, prompting the user to avoid these combination.