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 one-compartment model was detected. The doubled-peak phenomenon was identified after oral administration and the 1^st peak concentration (C_max1) and the 2^nd peak concentration (C_max2) in plasma were 2.29±0.46 and 1.68±0.33µg/mL at 1^st and 8^th h respectively, the absorption half-life (t_1/2ka) was 0.045 h, the elimination half-life  (t_1/2ke) was 5.81 h, systemic total body clearance (Cl) was 0.72 mL/h/kg, volume of distribution of the central compartment (V_d/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.