Ketorolac tromethamine (KT) is considered as a member of NSAIDs that used in treatment of rheumatoid arthritis. The main problems associated with the frequent administration of KT orally could be overcome by alternative routes as topical application. KT was formulated in different topical formulations such as gels, emulgels and creams. Sodium carboxymethylcellulose, carbopol 934 and pluronic F127 were used as polymers. In vitro permeation study through rat skin was carried out. The effect of different KT concentrations and the effect of skin penetration enhancer on the amount of KT permeated were investigated. Anti-inflammatory activity using commercial piroxicam gel for comparison was evaluated. The effectiveness and tolerability of the selected KT gel and piroxicam gel in osteoarthritis patients was also studied. The results obtained showed that, the flux of the drug increased with increasing its initial concentration. Using sodium lauryl sulfate as enhancer resulted in an improvement of KT permeation through rat skin. All formulations had the potential for local applications of KT as anti-inflammatory drug as compared to the control group. There was no significant difference in the efficacy between the selected KT gel and piroxicam gel for osteoarthritis patients. So KT gel may be used as another therapeutic option for the treatment of patients with osteoarthritis.