This work was performed to quantitatively determine doxycycline residues in different tissues of rabbits (kidneys, spleen, liver, muscles, heart and lungs) and sera following multiple oral doses of the drug using High Performance Liquid Chromatography. Moreover, the study aimed to estimate the withdrawal time of this drug in rabbit tissues. Twenty five healthy male New Zealand rabbits ranging from 2-2.5 kg body weight were used. Twenty one rabbits were given doxycycline directly into the stomach at a dosage of 10 mg/kg BW once daily for five successive days. Samples were analyzed at 1^st, 3^rd, 5^th, 7^th, 9^th, 15^th and 21^st day after last oral dose. The results indicated a widespread distribution of doxycycline in the samples, which remained within the detectable limit till the 3^rd day in most tested tissues. While in kidneys, spleen and liver, doxycycline remained till the 5^th day following the last oral administration of the drug. Therefore, it is recommended that rabbits treated with doxycycline must be slaughtered after the fifth day of drug administration to be safe for human consumption.