Non-steroidal Anti-inflammatory Drugs (NSAI Ds); are chemically heterogeneous large groups of drugs which suppress inflammation in a manner similar to steroids, but with less side effects of sedation, respiratory depression, or addiction than steroids. Piroxicam is used in the treatment of osteoarthritis, dysmenorrhoea, and pyrexia and as an analgesic. Piroxicam selectively inhibit cyclooxygenase-2 over than cyclooxygenase-1 enzymes. This work aimed to study the biochemical changes associated with administration of non-steroidal anti-inflammatory Piroxicam in breeding rabbits. The present work was carried-out on 27 apparently healthy native male rabbits about 3 months' age and 975 gm average weight. Results showed significant decrease in RBCs, Hb and PCV values. On the same, sever and significant decrease in total WBCs and neutrophils when injected the anti-inflammatory by over dose of the drug at all the three periods of experiment. There was significant decrease in Ca. Ph., Mag. levels .Over dose resulted in severe decrease in above elements. Also significant decrease of the copper, zinc and iron especially at the over dose Compared with control group. Blood glucose and serum protein showed non-significant changes, compared to control group. On the other hand there was a significant increase in the activities of Aspartate amino transferase (AST), Alanine aminotransferase (ALT) and Alkaline phosphatase (ALP) especially over dose of the drug. Kidney function tests showed a significant increase in both urea and creatinine especially in over dose treatment group. Also, the cholesterol level appeared as in high level in all treated group all over the period of research. Significant increase of alkaline phosphatase activities and zinc in both therapeutic and over dose along the course of the study were observed except the gradual decrease of the zinc in the testes homogenate. Nephro, hepato- and hemato-toxisity could induced by piroxicam treatment of rabbits specially by over dose (1 mg /kg.bw.) which should be avoided in field treatments of animals (rabbits)