Background: Prednisolone acetate is a glucocorticoid used to treat steroid-responsive inflammation repeatedly during the day, and the primary concerns with its 1% suspension and 0.5% commercial ointment include impaired vision and poor patient compliance. Objective: The aim of the current study was to create a prednisolone acetate ophthalmic microemulsion-loaded gel to improve dose accuracy, bioavailability, and consequently the efficacy of prednisolone acetate in treating inflammatory ocular disorders and patient adherence. Material and methods: A unique formulation was created by combining prednisolone acetate microemulsion with a different gelling agent to create a microemulsion-loaded gel. Results: The melting points determined from differential scanning calorimetry (DSC) and the capillary tube technique are extremely close to the standard, indicating the purity of the prednisolone acetate utilized. The best recipe (G2), a microemulsion-loaded gel with 1% carbopol934, had a white milky hue, high homogeneity, spreadability, and gelling capability. The drug content was 99.76%. The pH of the produced gels is comparable to that of eye tears and is not irritating to the eye. The FTIR data show that there is no interaction between the pure medicines and any of the excipients. When integrated into an optimal microemulsion-loaded gel formulation, drug release as obtained in Sorensen phosphate buffer saline (pH 7.4) attained an average of 97.51% in 8 hours. Ex vivo permeation studies further validated the two-fold increase in drug flow through the cornea from MEs-loaded gel compared to marketed ointment. Conclusion: Prednisolone acetate microemulsion-based gel (G2) ocular drug delivery system provides a potential strategy for enhancing corneal contact, penetration, and flux for ME-loaded gel formulations compared to the control; Extended precorneal retention in the eye resulting in prolonged medication release, increased bioavailability, and patient compliance.