Considering the properties of heterogeneity and anisotropy of wellbore skin, a mathematical model for the unsteady 3D flow in an anisotropic confined aquifer with two radial layers is developed. Using the Laplace transform technique and matrix theory, the solutions of drawdown for skin zone and formation zone, as well as the distribution of flux along well screen, are derived. Basing on the derived solutions, a numerical program is developed, and the flow subjected to stochastic change of permeability of layered skin zone is analyzed. The results indicate that: the vertical distribution of drawdown within skin zone and its vicinity, as well as the flux along well screen depend on the vertical heterogeneity of skin zone. While the influence range of skin zone is closely related with the vertical permeability of confined aquifer. Improvement of permeability or increasing thickness of negative skin can effectively raise well production. The magnitude of drawdown is mainly decided by the vertical permeability of formation zone and less influenced by the radial permeability of formation zone when radial permeability in skin zone is low, while the drawdown is obviously affected by not only the vertical permeability but also the radial permeability of formation zone when radial permeability in skin zone is comparatively large.