Abstract: Degradation of dexamethasone (DXM) is inevitable in the release test of dexamethasone implants (DI). In the release test conducted with flow-through cell method, the measured release curves of DI started to fall when cumulative release reached 70%-80%. Studies have shown that DI demonstrates a zero-order release rate of drug within every sampling interval, and a zero-order rate degradation in water (containing 0.05 mg·mL^-1 benzalkonium chloride). Hence, this study establishes a double zero-order model (DZOM) to calculate the release during sampling intervals with the formula R_i = R_im-R_(i-1)m×(C_in/C_i0)×2/(1＋C_in/C_i0). At each sampling interval, we measure the initial and final drug contents in the release medium, and the concentrations of the active pharmaceutical ingredient (API) in the release medium obtained at the same condition of release test, to calculate the total released DXM from the implants including the degraded drug. This paper has also analyzed the reasons for the fluctuations in the drug release curve and the errors in the DZOM and provided solutions. Experimental results show that the DZOM has effectively solved the problems encountered in the normal release method (NRM). The DZOM can be a potential solution to drug degradation problems in the release tests of long-acting injections.