AbstractNaturally occurring biomaterial scaffolds derived from extracellular matrix (ECM) have been the topic of recent investigation in the context of rotator cuff tendon repair. We previously reported a method to treat fascia ECM with high molecular weight tyramine substituted‐hyaluronan (TS‐HA) for use as a tendon augmentation scaffold. The presence of crosslinked TS‐HA in fascia was associated with an increased macrophage and giant cell response compared to water‐treated controls after implantation in a rat abdominal wall model. The objective of this study was to determine the extent to which TS‐HA treatment was associated with mechanical property changes of fascia after implantation in the rat model. Fascia samples in all groups demonstrated time‐dependent decreases in mechanical properties. TS‐HA‐treated fascia with crosslinking exhibited a lower toe modulus, a trend toward lower toe stiffness, and a higher transition strain than water‐treated controls not only after implantation, but also at time zero. TS‐HA treatment, with or without crosslinking, had no significant effect on time‐zero or post‐implantation load relaxation ratio, load relaxation rate, linear‐region stiffness, or linear‐region modulus. Our findings demonstrated that the particular TS‐HA treatment employed in this study decreased the low‐load elastic mechanical properties of fascia ECM, in keeping with the heightened macrophage and giant cell host response seen previously. This work provides a starting point and guidance for investigating alternative HA treatment strategies. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.