Background: Orbifloxacin is being widely used in China to treat fish infections in an extra-label manner, which may cause its potential residues in edible tissues. Aims: The purpose of this study was to determine the disposition kinetics of orbifloxacin in CRUCIAN CARP (Carassius auratus) following intramuscular administration for its further safe application in aquaculture industry. Methods: Tissue samples of skin, muscle, kidney, and liver were collected from six CRUCIAN CARPs reared at 25° C at 5, 10, 15, 30, 45 min, 1, 2, 4, 6, 12, 24, 48, 72, and 96 h following a single intramuscular injection at 7. 5 mg/kg body weight (BW). The orbifloxacin concentrations in tissues were determined using a high-performance liquid chromatography (HPLC) method with a fluorescence detector, then average concentrations versus time data were subjected to non-compartmental analysis to obtain the kinetic parameters. Results: The peak concentration of 5. 68 ± 0. 03 μ g/g was calculated in kidney at 2 h, followed by muscle (5. 51 ± 0. 01 μ g/g) at 4 h, liver (4. 84 ± 0. 20 μ g/g) at 2 h, and skin (4. 27 ± 0. 08 μ g/g) at 4 h. Area under concentration-time curve was calculated as 79. 22, 94. 72, 118. 65, and 129. 02 h· μ g/g in kidney, liver, skin, and muscle, respectively. And the elimination half-lives were determined as 18. 17, 18. 41, 18. 77, and 19. 11 h in skin, kidney, muscle, and liver, respectively. Conclusion: It was shown that orbifloxacin was well distributed into tissues while relatively slowly eliminated in CRUCIAN CARP reared at 25° C following a single intramuscular injection.