Objective To investigate the efficacy of a new collagen-hydroxyapatite（COL-HA） composite membrane on bone regeneration of SD rat cranial defects. Methods Four defects were produced in the calvaria of 24 SD rats. The animals were divided into four groups: Empty defects without membrane（group 1）; defects covered by COL-HA single-layer dense membranes（group 2）; defects covered by COL-HA double-layer membranes（group 3）; defects covered by Bio-Gide membranes（group 4）. At 2, 4, 8 and 12 weeks after surgery, 6 rats were sacrificed and the following parameters were analyzed: Macroscopic observation, X-ray examination, descriptive histology, regenerate bone quantitative histology. Statistical analysis consisted of generalized linear models/factorial design analysis of variance and LSD-t test was performed. Results Since two weeks after surgery, there were a small amount of bone regenerated in three groups except group 1. At 12 weeks after surgery, the opaque sclerous tissues filled with the defects in three groups, and residual membrane fragments still could be found. X-ray pictures showed the density of regenerate bone in group 3 and group 4 was closed to the original bone and greater than that of group 2. Quantitative analysis of regenerate bone showed that in initial stage, group 4 had more bone regeneration than the other groups（P
