Danofloxacin is a new generation fiuoroquinoione antibiotic. There is limited literature information regarding its toxicity with long-term use. Therefore, likelihood of adverse effects increases. This study was aimed to determine the effects of long-term danofloxacin administration at different doses primarily on serum oxidative stress parameters, as well as biochemical and complete blood count parameters. Forty rats were divided into four groups with equal numbers in each group. While rats in the control group were not subjected to any treatment, other three groups received 5, 10, and 25 mg/kg of danofloxacin (intraperitoneal) daily for three weeks, respectively. At the end of the experiment, the animals were anesthetized, blood samples were collected and they were euthanized. The collected blood samples were centrifuged to separate the serum fractions. Serum levels of oxidative stress parameters (maiondiaidehyde, superoxide dismutase, glutathione peroxidase) were determined using the Enzyme-Linked Immunosorbent Assay reader. Levels of serum biochemistry parameters (aspartate aminotransferase, gamma glutamyl transferase, blood urea nitrogen, cholesterol, phosphorus, magnesium) were measured using an autoanalyzer. Hemogram parameters (white blood cell, red blood cell, platelet, hematocrit, hemoglobin) were measured using a hemocell counter device. In the study, administration of danofloxacin for 21 days at different doses had no effect on oxidative stress and hemogram parameters (P > 0.05). However, high doses (10 and 25 mg/kg) of danofloxacin elevated aspartate aminotransferase, gamma glutamyl transferase, cholesterol, and phosphorus levels (P < 0.05). In conclusion, long-term administration of danofloxacin does not cause oxidative stress or affect hemogram parameters; however, patients should be monitored for liver and kidney function and lipid metabolism. Furthermore, more studies using histopathological or molecular methods involving disease models are needed to determine the extent of organ damage in the future.