Abstract: In this study, we established an optimization control model and the corresponding computer algorithm to estimate the diffusion coefficient of the drug releasing in the spherical device. First, based on the diffusion equation in the spherical device in the polar coordinates system, the optimal control model was given to compute the diffusion coefficient in the drug releasing problem in the sphere device. Next, the Least Square Method based on the Separation Variables (LSMSV) was used to solve the problem to estimate the appropriate diffusion coefficient. Finally, a numerical example was presented to show that the control model and the numerical method are valid for computing the diffusion coefficient of the drug releasing in the sphere device.