Background: Retinal ganglion cell loss may occur as a result of gradual damage to the ocular nerves in glaucoma, a group of eye diseases. Glaucoma is one of the main causes of blindness worldwide. The only method to stop the progression of the condition is to decrease IOP. New therapeutic approaches are continually being developed to actualize the advancements in glaucoma therapy. These therapies will provide specific tissue objectives to lower IOP. Nesiritide is a natriuretic peptide that is effective in reducing blood pressure via his vasodilator action which may be effective in reducing intraocular pressure.Aim of the Study: To evaluate the efficacy of topically applied nesiritide (0.015%) eye drops on IOP of ocular normotensive and betamethasone-induced ocular hypertensive in comparetion with that of latanoprost (0.005%) eye drops, besides, to study the safety profile of these nesiritide eye drops.Materials and Methods: This study included 36 male rabbits; out of the total, 18 rabbits represented the ocular normotensive groups (Control group, Latanoprost group, and Nesiritide 0.015% group) and the other 18 rabbits represented betamethasone-induced ocular hypertension groups (vehicle group, Latanoprost group, and Nesiritide 0.015% group). Tested drugs instilled as one drop (50 mu l) twice daily for 7 days in normotensive and hypertensive left eye. The intraocular pressure was measured for the eyes with the aid of Schiotz tonometer according to the instructions of manufacturer. The other examined parameters were pupil diameter, light pupillary reflex, corneal sensation reflex, and conjunctival redness. These parameters were recorded before starting the experiment and then daily before and after drug application.Results: This study revealed that nesiritide eye drops in (0.015%) concentration significantly accelerated reduction of intraocular pressure in rabbit model and significantly reduced IOP on the second day in both normotensive and steroid-induced ocular hypertensive model. That these results were comparable to the lowering effect of latanoprost (0.005%)eye drops that reduced IOP significantly on the second day in both normotensive and ocular hypertensive rabbits. The other examined parameters that included pupil diameter, light pupillary reflex, corneal sensation reflex, and conjunctival redness showed no change or difference with using nesiritde eye drops in (0.015%) concentration.Conclusion: The present study revealed the concentration-dependent efficacy of topically applied nesiritide eye drops in lowering of IOP in both ocular normotensive and betamethasone-induced ocular hypertensive rabbits; furthermore, efficacy of nesiritide (0.015%) eye drops was found to be comparable to that of latanoprost (0.005%) eye drops. Besides, the present study proved the safety of nesiritide eye drops in (0.015%) concentration without detectable side effects.