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In this work, the non-linear vibrations of a simply supported fluid-filled orthotropic cylindrical shell subjected to axial and lateral time-dependent loads are analyzed. To model the shell, the Donnell nonlinear shallow shell theory without considering the effect of shear deformation is used. The fluid is assumed to be incompressible and non-viscous and the flow to be isentropic and irrotational. A model with eight degrees of freedom is used to describe the lateral displacements of the shell and, the Galerkin method is applied to derive the set of coupled non-linear ordinary differential equations of motion. Five different orthotropic materials are analyzed. Results show that the material orthotropy and geometry parameters have a strong influence on the critical loads, natural frequencies, post-buckling paths and frequency-amplitude relations.