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<b>Purpose: </b> Candidal endophthalmitis is a sight-threatening ocular infection that most frequently occurs as a complication of candidemia. Fluconazole has been effective against <i> Candida albicans</i> in various animal models. Our objective was to evaluate retinal toxicity of plain and liposome formulation of fluconazole at various dose levels after intravitreal injection. <b> Materials and Methods: </b> Twelve New Zealand albino rabbits weighing 2-2.5 kg were used. Two rabbits were used for every dose level. Liposome formulation containing 100 and 200 &#x00B5;g of fluconazole in sterile phosphate buffer solution and plain fluconazole at concentrations of 100, 200, 400 and 800 &#x00B5;g in 0.1 ml of sterile normal saline were injected intravitreally into the right eyes. The left eyes received 0.1 ml normal saline or 0.1 ml of liposome formulation without fluconazole. One week later, the animals were sacrificed, their eyes enucleated and processed for light microscopy and scanning electron microscopy. <b> Results:</b> It showed that plain fluconazole at a concentration of 100 &#x00B5;g and above caused retinal changes, with disorganization of the photoreceptor outer segments. However, liposome formulation of fluconazole (200 &#x00B5;g/0.1 ml) did not show any significant microscopic changes of the retina. <b> Conclusion: </b> The liposome formulation decreased the retinal toxicity of fluconazole up to the studied concentration of 200 &#x00B5;g/0.1 ml.