This experiment was carried out on 24 guinea pigs and 54 male rats. Both rats and guinea pigs were divided into 3 equal groups. Animals in group 1 served as control. Those in second and third groups were injected i.m. with danofloxacin in doses of 5 and 10 mg/kg b. wt. respectively for 5 consecutive days. The obtained results revealed that danofloxacin (10 mg/kg b. wt. i. m.) after the 5th day post dosing induced significant decrease in bile flow in both rats and guinea pigs. Serum levels of alanine aminotransferase (ALT), urea and creatinine were significantly elevated after the 1st and 5th days Post dosing at the two dose levels. Furthermore the values of aspartate aminotransferase (AST) were significantly increased after 1st day post dosing of therapy. Serum glucose and calcium levels Were insignificantly changed after drug administration. Danofloxacin (5 mg/kg b. wt. i. m.) significantly decrease paked cell volume (PCV%) and red blood corpuscles ( BBCs) count after 1st day post dosing. Meanwhile, it evoked a significant decrease in haemoglobin (Hb) contents , PCV% and RBCs count after 1st day post dosing at the dose level of 10 mg/kg b. wt. i. m. Danofloxacin has no effect on the motility of isolated rabbit duodenum and guinea pig ileum. Concerning the genotoxic effect of the drug on bone marrow cells, the results revealed that danofloxacin has no significant effect on the rate of mitotic division at a dose level of 5 mg/kg b. However, it produced a highly significant decrease in the rate of mitosis at a dose of 10 mg/kg b. wt. Moreover. The drug induced a significant increase of structural chromosomal aberrations. The percentage of aberrations were 18.4 and 26.6 for 5 and 10 mg/kg b. wt. as compared with 2% for control non treated group. The structural chromosomal aberrations induced by danofloxacin were fragments, deletion, ring chromosome, gaps, breaks and chromosomal stickiness.