Mefenamic acid is a non-steroidal anti-inflammatory agent. Oral administration of this drug is associated with severe gastrointestinal side effects like ulceration and gastro intestinal bleeding. The solution of this problem lies in the fact that, topically applied NSAIDs are safer than oral NSAIDs. The objective of the study was to prepare an ointment of Mefenamic Acid by using different penetration enhancers such as propylene glycol, Sodium lauryl sulphate, tween80 and ethanol. Evaluation of the Mefenamic Acid ointment was carried out for physical appearance, pH, spreadability, extrudability, drug content and in-vitro release. Drug content was found to be uniform in all the formulations. The result shows that ointment have good consistency, Spreadability, and formulation F1 and F2 with propylene glycol and sodium lauryl sulphate respectively shows good diffusion rate than others.