AIM: To investigate the bio-colonization of poly 2-hydroxyethy methacrylate (PHEMA) sponge with cornea tissue and evaluate the therapeutic effects of modified porous poly 2-hydroxyethy methacrylate-Polymethyl methacrylate (PHEMA-PMMA) Keratoprostheses (KPro) on rabbit and monkey corneas. METHODS: The KPro were made using two-stage polymerization combined with mechanical cutting. The experiments were divided into two groups. In the control group, ten normal rabbit eyes received lamellar implantation of PHEMA sponges. The sponges were obtained 2 weeks, 1, 2, 3 and 4 months after operation. The cell proliferation and neovascularization inside the sponges were observed using light and transmission electron microscopy (TEM) and immunohistochemistry. In the experimental group, the porous PHEMA-PMMA KPros were inserted into the lamellar pockets of eight rabbit corneas and two monkey corneas (stage I operation). The healing process was investigated by slit-lamp microscopy. The anterior lamellar cornea tissues were removed 3 months after surgery, exposing the underneath transparent core (stage II operation). The operated eyes were then followed up for 3-6 months. RESULTS: No complications were observed in the control group. Under the light microscope, fibroblasts started to grow into the cornea 2 weeks after operation; lots of cells, accompanied with new blood vessels, invaded into the cornea 2-3 months after surgery. Invading cells of sponge, as well as keratocytes, were positive for vimentin. Under the electron microscope, the invading cells looked healthy and were surrounded by extracellular matrix and collagen. In eight rabbit eyes which received KPro implantation, anterior lamellar cornea melting happened in two eyes after the stage II operation. The remaining six corneas retained their central cores during observation after the stage II operation. Two operated monkey eyes were found no complication throughout the whole follow-up. CONCLUSION: The PHEMA sponge can obtain a tight fusion with the host cornea. The modified PHEMA-PMMA KPros have obtained relatively stable results after implantation into animal corneas. "