To assess potential effects of hyperbaric oxygen (HBOT) on artificial bone grafts, beta-Tricalcium phosphate (beta-TCP) and calcium phosphate coated bovine bone (CPCBB) substitutes were applied to standard bone defects in rat tibiae. The control defects were left empty. Half of the animals received 60 minutes of 2.4 atmosphere absolute (ATA) of HBOT. Rats were sacrificed at one, two and four weeks. Bone healing was assessed histologically and histomorphometrically using light microscopy. The periosteum over the bone defects was examined ultrastructurally. Cardiac blood was collected to determine the serum osteocalcin levels. The HBOT increased new bone formation in the unfilled controls and beta-TCP groups and significantly decreased cartilage matrix and fibrous tissue formations in all groups. Active osteoblasts and highly organized collagen fibrils were prominent in the periosteum of beta-TCP and control groups. Serum osteocalcin levels also increased with HBOT. The healing of defects filled with CPCBB was similar to the controls and it did not respond to HBOT. These findings suggested that the HBOT had beneficial effects on the healing of unfilled bone defects and those filled with beta-TCP bone substitute but not with CPCBB, indicating a material-specific influence pattern of HBOT.