Diclofenac sodium is one of the non-steroidal anti-inflammatory drugs (NSAIDs), which is used for treatment of rheumatic diseases and pain relieve.The current study aimed to determine diclofenac sodium residues in different rabbit tissues (liver, muscles, kidneys, spleen, heart and lungs) following its intramuscular injection. Tissues were extracted and diclofenac residues were assayed using high performance liquid chromatography (HPLC). A total of twenty healthy male New Zealand white rabbits were divided into two groups; the first group (n=15) was intramuscularly injected with diclofenac sodium for four successive days at a dose of 1.5mg/kg body weight (BW) twice daily, while the second group (n=5) remained untreated (negative control). The samples were collected at the 1 st day, 3 rd day, 5 th day and 7 th day post injection. The results showed that diclofenac remained within the detectable limit till the 3 rd day post injection in serum (0.0227±0.05 µg/mL) and rabbit issues as liver, heart, lung and spleen (0.043±0.078 µg/g, 0.146 ±0.064 µg/g, 0.043±0.012 µg/g and 0.075±0.035 µg/g, respectively) but it remained in muscles (0.034±0.0603 µg/g) and kidneys (0.0507±0.0146 µg/g) till the 5 th day following the last dose of drug administration. In conclusion, rabbits treated with diclofenac must be slaughtered after the 5 th day from last dose of repeated administration for complete withdrawal of diclofenac residues from all tissues of treated rabbits to be safe for human consumption.