Ethoniosomes (EVs) composed of span 60: CH (7:3) containing 20% (v/v) ethanol and prepared by TFH method was prepared and tested for its irritation potential to the ocular tissue and its in vivo anti-inflammatory activity compared to commercial products. Also, the duration of action of the prepared EVs was determined. In addition to, measurement of the cumulative increase in the IOP for both; the prepared EVs and the conventional formulations. The results showed that, no signs of irritation were observed for either the cornea or the conjunctiva. The ocular anti-inflammatory activity of EVs entrapping Pred A and Pred P was significantly higher compared to conventional formulations. The cumulative IOP of TFH-EVs entrapping either Pred A or Pred P showed smaller increase in IOP compared to conventional formulations. Further, an obviously prolonged absorption and relatively slower elimination rates were demonstrated for Pred A EVs, Pred P EVs formulations. In conclusion, EVs may serve as a novel delivery system improving the ultimate outcome any drug can offer; which is high efficacy in terms of activity and duration of action and a lesser side effects in terms of IOP raising potential