Chondroitin sulphate (CS) has an anti-inflammatory effect and increases the regeneration ability of injured bone. The goal of this study was to characterize the material properties and osteoconductive potency of calcium phosphate bone cements modified with CS. The early interface reaction of cancellous bone to a nanokristalline hydroxyapatite cement containing type I collagen (HA/Coll) without and with CS (HA/Coll/CS) in a rat tibia model was evaluated. Cylindrical implants were inserted press-fit into defect of the tibial head. Six specimens per group were analyzed at 2, 4, 7, 14, and 28 days. HA/Coll/CS composite cylinders showed a 15% increase in compressive strength and by investigations with powder X-ray diffraction more non-transformed cement precursor was found. The microstructures of both types of implants were similar. A significantly higher average number of TRAP positive osteoclasts and ED1 positive mononuclear cells were observed in the interface around HA/Coll/CS implants on day 4 and 7 (p < 0.05). At 28 days the direct bone contact and the percentage of newly formed bone were significantly higher around HA/Coll/CS implants (p < 0.05). The addition of CS appears to enhance bone remodelling and new bone formation around HA/Coll composites in the early stages of bone healing. Possible mechanisms are discussed.