Articular cartilage is a highly differentiated tissue, lacking a vascular supply and having only limited regenerative capability. Cut or other mechanical damage restricted to the cartilage does not repair. Experimentally and clinically, cartilage defect that penetrate the subchondral bone undergoes repair through the formation of tissue usually characterized as fibrous, fibrocartilaginous or hyaline-like cartilaginous tissue. There is little definitive informations about local or systemic factors that control the differentiation of mesenchymal cells to osteoblast, chondroblast or fibroblast. Our study was designed to evaluate the effect of transforming growth factor-beta (TGF-pl) and autogenous periosteal graft on the healing of osteochondral defect of distal femur of rabbit and also the possibility of these method to be clinically applicable to human. The experimental model used in the present study for including cartilage in rabbit was based mainly on the model used by Frukawa et al14). in rabbit. A full thickness osteochondral defect of 80 rabbit were made with 2mm diameter of drill-bit and electrically driven drill. Experimental animals were divided into four group: 1) group I, osteochondral defect only, 2) group II, osteochondral defect with infiltration of phosphate buffer solution, 3) group III, osteochondral defect with infiltration of TGF-Bl, 4) group IV, osteochondral defect with autogenous periosteal graft. The healing of the defect was assessed at 1 week, 3 weeks, 5 weeks, 12 weeks after operation by gross and histochemical examination. At 1 week, fibrinoid material in edge to edge arcade arrangement was present in group I,II,III,IV. At 3 weeks, spindle shaped undifferentiated mesenchymal cell present in the periphery of fibrinous network, but there is no appearance of mesenchymal cell in group I,II. At 5 weeks, essentially complete repopulation of the defect with progressive differentiation of cells to chondroblast, chondrocyte, osteoblast and synthesis of cartilage and matrix in their appropriate location in group III and IV were found. At 12weeks, hyaline like cartilage formation was observed in group III and IV. but early trace of degeneration of the cartilage were seen in many defect with the prevalence and intensity of the degeneration increasing at group I and 3 . Our study demonstrated in detail the repair of full-thickness defect in rabbit articular cartilage extending into cancellous bone of the marrow cavity under influence of local growth factor (TGF-pl) and autogenous periosteal graft. Excellent reconstruction of articular cartilage was observed in TGF-Bl infiltration group and autogenous periosteal graft group as early as 5 weeks after the creation of defect. Although the further study should be carried out for their clinical application, we conclude that TGF-Bl regulates the overall mechanism of matrix constituent in connective tissue and autogenous periosteal graft have a chondrogenic potential to repair major osteochondral defect. these suggest that TGF-Bl and autogenous periosteal graft may be a important pathophysiological regulator of chondro-genesis.