African catfish (Clarias gariepinus) aquaculture has experienced widespread production and has lately gained considerable interest in Egypt. Doxycycline (DOX) is used to control certain common fish's bacterial diseases, such as Septicemia, Fin rot, Columnaris, and Tail Rot. Therefore, our experiment was conducted to assess the pharmacokinetic properties of single doxycycline dose (20 mg/kg BW) orally administered in the African catfish. DOX plasma levels were measured using HPLC with a limit of detection nearly 0.035 μg/ ml, and then were undergoing compartmental analysis; a onecompartment model was detected. The doubled-peak phenomenon was identified after oral administration and the 1st peak concentration (Cmax1) and the 2nd peak concentration (Cmax2) in plasma were 2.29±0.46 and 1.68±0.33μg/mL at 1st and 8th h respectively, the absorption half-life (t1/2ka) was 0.045 h, the elimination half-life (t1/2ke) was 5.81 h, systemic total body clearance (Cl) was 0.72 mL/h/kg, volume of distribution of the central compartment (Vd/F) was 5.74±1.11 L. These findings suggested that DOX was to some extent rapidly absorbed, widely distributed, and slowly excreted; moreover, it could be subjected to enterohepatic recycling.