Zirconium alloys used as cladding tubes for the fuel of Pressurized Water Reactors can undergo high applied stress during power transients. In these conditions, biaxial loading may lead to plastic deformation of the cladding. A comprehensive understanding of the material mechanical response during loading-path change tests is an important step toward the prediction of the behavior in these specific conditions. Using a non-standard mechanical testing machine, loading-path change tests have been conducted at 623 K on as-received recrystallized Zircaloy-4 tubes. These tests consist of an axial tensile loading and unloading followed by an internal pressure (or pure hoop tension) loading and unloading. These tests are able to examine the kinematic and isotropic hardening components of the strain hardening behavior of the thin cladding tubes. The isotropic hardening is attributed to dislocation multiplication and dislocation-dislocation interactions. The kinematic hardening is attributed to the interaction of the grains with each other. A polycrystalline model has also been used and improved in order to simulate the tests. A good prediction of the isotropic and kinematic hardening is provided by the modeling.