Tetracycline is one of the most important groups of antibiotics that have harmful effects on the consumers, therefore the public health safety against its residues represents a significant issue. This study aimed to estimate the effect of tetracycline hydrochloride on some hematological parameters, kidneys function tests as well as liver and breast muscle enzymes with special reference to the supposed withdrawal time of this drug in different rabbits’ tissues (kidney, liver and muscles), following oral dose of tetracycline using High Performance Liquid Chromatography. Tetracycline was administrated to eighteen rabbits directly into the stomach at a dose of 35 mg/kg BW once daily for five successive days. Samples were collected on the 1st, 3rd, 7th, 14th, 21st and 28th days after the last oral dose. The results revealed that, tetracycline caused a significant increase in the uric acid, urea, creatinine, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) activities with no significant changes in the hematological parameters when compared with the control group. The residues remained in the liver and kidney for 7 days, while in muscles for 3 days only after the last oral dose of the drug. In conclusion, the disturbances in the biological parameters occurred by tetracycline administration in rabbits was transient and returned to normal after 7 days of last treatment. The withdrawal time of tetracycline was 14 days from the rabbit's tissues.