Objective: To evaluate the barrier effect of an absorbable barrier membrane made by small intestinal submucosa (SIS) compared with Bio-Gide collagen membrane. Methods: 12 healthy New Zealand male white rabbits were randomly assigned. A or B round bone defects with a depth of 2 mm and a diameter of 5 mm or 8 mm was made in each rabbit’s mandibular. The following treatments were given respectively: covered with SIS membrane (S), covered with Bio-Gide membrane (G) and blank control (O). Then we got six groups: AS, AG, AO, BS, BG, and BO (n=4). After 4 weeks, the rabbits were sacrificed. The specimens were examined by naked-eye observation, new bone percentage (BV/TV) and bone mineralized density (BMD), which were measured and analyzed by Micro-CT. The data were analyzed with one-way ANOVA. Results: After 4 weeks, Bio-Gide membranes were fused with the surrounding tissue while SIS membranes held the form with no significant degradation. In the AS, BS and AG groups, the absorbable membranes smoothly covered on the new bone. While in the BG group, Bio-Gide membranes collapsed to the center of the bone defects. The 3D reconstruction of Micro-CT showed that a large number of newly formed trabeculae were found in the four groups of AS, BS, AG, and BG. In the central subsidence area of the BG group, the newly formed trabeculae were sparse. However only a small amount of new bone trabecula appeared at the bottom of the defects in groups AO and BO. Micro-CT quantitative results showed that BV/TV (39.10%±0.79%) and BMD [(517.73±11.22) mg/cm ³] of AS group were significantly higher than those of AO group [26.67%±1.12%, (319.81±8.00) mg/cm ³] (P < 0.05), and there was no significant difference between AS group and AG group [38.15%±0.91%, (518.65±7.48) mg/cm ³] (P>0.05). BV/TV (34.90%±1.35%) and BMD [(409.09±8.14) mg/cm ³] of BS group were significantly higher than those of BO group [23.63%±2.07%, (171.00±16.24) mg/cm ³] (P < 0.05). Meanwhile, there was no significant difference between BS and BG groups [33.40%±1.06%, (412.70±8.6) mg/cm ³] (P > 0.05). HE staining analysis revealed that significant bone formation was achieved in the AS, AG, BS and BG groups, and trabecular bone of AS and AG groups were thicker and denser. In AO and BO group, there were scattered new bone tissues in edges of host bone, and no coarse trabecular bone formed. Conclusion: In the early healing of two sizes bone defects in rabbit mandibular, SIS membrane and Bio-Gide membrane have a similar barrier effect in guided bone regeneration. And SIS membrane's ability to maintain space for bone regeneration seems to be better.