Objective To compare and evaluate the differences of potentialities, biological characteristics and results between periosteum transplant, cartilage transplant and subchondral bone drilling in repairing full-thickness defects of articular cartilage in weight-bearing joints, for the purpose of proposing the experimental basis for clinical application. Methods By using the repeated measure design of Latin Square, 32 adult male rabbits were divided into groups randomly based on three factors and four levels. Autologous periosteum transplant, allogenic cartilage transplant and subchondral bone drilling were applied for repairing of size-matched, full-thickness articular cartilage defects on the femoral condyle of the knees. The reconstructed tissues were observed by gross, optical and electronic microscopic view and analysed morphologically at 2, 4, 8, 12 weeks respectively. Results All of these three methods could repair the lesions by hyaline-like cartilage at 12 weeks, while the control groups were filled with fibrous tissue. The height of the repairing tissue compared with the normal cartilage and the light density data indicated that the cartilage transplant groups were better than others; periosteum transplant and bone drilling groups were better than the control groups as well. No evidence of immune rejection was observed. Based on the statistical analysis, the lesion size was not a significantly important factor for the repair. While the time was in a contrary way. Conclusion Autologous periosteum transplant, allogenic cartilage transplant and subchondral bone drilling are feasible for repairing of the full-thickness articular cartilage defects. These methods are beneficial options for clinical application, among which cartilage transplant is the best. The reconstructed tissue of subchondral bone drilling is insufficient for bigger defects.