To characterize the material properties of posterior and peripapillary sclera from human donors, and to investigate the macro- and micro-scale strains as potential control mechanisms governing mechanical homeostasis. Posterior scleral shells from 9 human donors aged 57-90 years were subjected to IOP elevations from 5 to 45. mmHg and the resulting full-field displacements were recorded using laser speckle interferometry. Eye-specific finite element models were generated based on experimentally measured scleral shell surface geometry and thickness. Inverse numerical analyses were performed to identify material parameters for each eye by matching experimental deformation measurements to model predictions using a microstructure-based constitutive formulation that incorporates the crimp response and anisotropic architecture of scleral collagen fibrils. The material property fitting produced models that fit both the overall and local deformation responses of posterior scleral shells very well. The nonlinear stiffening of the sclera with increasing IOP was well reproduced by the uncrimping of scleral collagen fibrils, and a circumferentially aligned ring of collagen fibrils around the scleral canal was predicted in all eyes. Macroscopic in-plane strains were significantly higher in peripapillary region then in the mid-periphery. In contrast, the meso- and micro-scale strains at the collagen network and collagen fibril level were not significantly different between regions. The elastic response of the posterior human sclera can be characterized by the anisotropic architecture and crimp response of scleral collagen fibrils. The similar collagen fibril strains in the peripapillary and mid-peripheral regions support the notion that the scleral collagen architecture including the circumpapillary ring of collagen fibrils evolved to establish optimal load bearing conditions at the collagen fibril level. © 2013 Elsevier Ltd.