Background and aim: Osteoarthritis (OA) is the most common joint disorder in the world.It is one of the most frequent causes of pain, loss of function and disability in adults. The currenttreatment of osteoarthritis is primarily focused on symptomatic relief by the use of rapidly actinganalgesics such as NSAIDs and newer cyclooxygenase-2(COX-2) specific inhibitors that havemany adverse effects. Hence, there is continuous search for new and better drugs for OAtreatment. Interleukin-1β plays an important role in the pathogenesis of OA. Diacerein, anInterleukin-1β antagonist has been used recently in treatment of OA. Accordingly this work wasdesigned to compare the anti-inflammatory effect of diacerein with one of the NSAIDs namelydiclofenac sodium and their combination on animal model of osteoarthritis, and to study theeffect of these drugs on systolic blood pressure.Experimental approach: 90 adult healthy female albino rats were allocated into 5 groups:normal untreated animals (negative control), the disease model group that received a single doseof monoiodoacetate (MIA) intra articularly in their right knees (positive control), and the (MIA)induced osteoarthritis treated either by diacerein, diclofenac sodium, or their combination for 6weeks. Level of serum cartilage oligomeric matrix protein as a specific biochemical marker forcartilage, histopathologic examination, and radiological assessment were performed to evaluatethe effect of the studied drugs. In addition a non-invasive measurement of systolic blood pressurewas done to study the effect of these drugs on systolic blood pressure.Results: Induction of OA by monoiodoacetate (MIA) resulted in development ofosteoarthritic changes detected by elevation of the biochemical parameter measured,deterioration of pathological scores and X-rays. Interestingly the administration of diacereinalone or with diclofenac sodium resulted in significant amelioration of all the parametersmeasured with no effect on systolic blood pressure. However, diacerein intake alone showed thebest results.Conclusion: The results of the present study revealed that diacerein has the potential toameliorate osteoarthritic changes with no effect on the blood pressure unlike the commonly usedNSAIDs.