In vitro drug release testing and ex vivo transcorneal drug permeation can provide valuable information on the performance of the Q1/Q2 equivalent ointments prior to any animal studies. Good correlation between in vitro and ex vivo drug release may be indicative of good in vitro and in vivo correlation. Accordingly, it is important to investigate in vitro as well as ex vivo drug release from Q1/Q2 equivalent ophthalmic ointments and evaluate whether a correlation between these release profiles can be established. Four Q1/Q2 equivalent loteprednol etabonate ointments were prepared using different processing methods and excipient sources. The rheological parameters (crossover modulus and K value) of the four formulations were determined. The in vitro drug release testing of the four ointment formulations were performed using three different apparati (Franz diffusion cells, USP apparatus 2 with enhancer cells and USP apparatus 4 with semisolid adapters). Three models (zero order, logarithmic and the Higuchi model) were used to study the release kinetics of the ointment formulations. The transcorneal (rabbit corneas) permeation studies were performed using spherical joint Franz diffusion cells. The USP apparatus 4 method demonstrated better discriminatory ability compared to the USP apparatus 2 and the Franz diffusion cell methods. The in vitro release profiles of the four Q1/Q2 equivalent ointments with manufacturing differences showed a better fit using the Higuchi model (R2 > 0.98) for all three release testing methods, compared to the other two models. Ex vivo drug release through the rabbit corneas displayed zero order release kinetics. A logarithmic correlation between rheological parameters (crossover and K value) and transcorneal flux were established. In addition, a plot of the in vitro release rate against the ex vivo release flux of the four ointment formulations, yielded a straight line (R2 > 0.98) for all three release methods. Accordingly, the rheological parameters may be useful in predicting in vitro as well as ex vivo release properties.