We performed this study to compare the intrascleral biocompatibility of three materials: non-absorbable hydrogel contact lens polymer, non-absorbable silicone rubber, and absorbable cross-linked sodium hyaluronate. Intrascleral implantation of three different materials was performed in 13 healthy, pigmented rabbits. Implants of methacrylic hydrogel, silicone rubber, and cross-linked sodium hyaluronate were implanted in 10, 8, and 8 eyes, respectively. The animals were euthanized at 7, 30, 180, and 360 days post implantation. The eyes were enucleated and immediately fixed in 10% buffered formalin. Semithin sections were cut and stained with hematoxylin-eosin. Light microscope analysis of the specimens was performed. The least severe inflammatory reaction was observed with cross-linked sodium hyaluronate implants. The number of inflammatory cells in proximity to methacrylic hydrogel and silicone implants at all periods of follow up was similar. The thickest fibrous capsule was observed with silicone implants (average, 28.38 +/- 11.17 microm). This area was thinner with methacrylic hydrogel implants (average, 14.90 +/- 5.57 microm) and was thinnest around sodium hyaluronate implants (average, 7.21 +/- 2.33 microm). For each type of implant, the wall on the conjunctival side of the fibrous capsule was significantly thicker than the wall on the choiroidal side. The space between the implant, scleral flap, and bed was filled soon after surgery with connective tissue rich in vessels. In our study, cross-linked sodium hyaluronate had the highest intrascleral biocompatibility. Although the inflammatory responses of the sclera to methacrylic hydrogel and silicone rubber were similar in nature, a thicker fibrous capsule was generated around silicone implants.