Diclofenac sodium is one of the non-steroidal anti-inflammatory drugs, which used in human and veterinary medicine frequently. This drug is effective in treatment of diseases such as, musculoskeletal derangement, rheumatoid arthritis and gout. However, the application of this drug has been limited due to its side effects include, gastrointestinal, renal and hepatic lesions. In this research 24 female 2 months old rabbit of about 1.6 kg weight were divided to 4 equal groups randomly and injected intramuscularly, once a day in a period of 10 days. In group 1 as control only normal saline was injected. Groups 2, 3 and 4 received the drug 1,1.5 and 2 mg/kg respectively. At the end of experiment, the animals were euthanized and macroscopic and microscopic lesions in stomach, kidney and liver were studied. Macroscopic inspections revealed congestion of the liver and kidney in group 3 and 4. However, histopathologic examinations showed not any lesion in group 1, lymphocytic hepatitis, fatty change of the liver and renal fibrosis in group 2, hepatic necrosis, lymphocytic hepatitis, glomerular atrophy, interstitial nephritis, renal fibrosis, thickening of the bowman s capsule, renal pelvis fibrosis and gastric edema in group 3 and glomerular atrophy, renal medullary and pelvis fibrosis, acute tubular necrosis, interstitial nephritis, giant cell formation, hepatitis and gastric edema in group 4. Inhibition of prostaglandins is the most important cause of these side effects. The present results have emphasized on usage the drug with precautionary measures.