Abstract: Objective: To investigate the changes of CaMKⅡexpression level in degenerative cartilage of rats mandibular condylar induced by unilateral anterior crossbite. Methods: Forty 6-week-old SD female rats were randomly and equally divided into UAC (unilateral anterior crossbite) group and the control group. Metal prosthesis was cemented to the left maxilla and mandible incisors of the UAC group rats to create the unilateral anterior crossbite relation. Animals were sacrificed at the end of the 4th or 8th week after stimulation of UAC. Hematoxylin-eosin (HE) and safranin O (SO) staining were carried out for studying the morphological changes of the condylar cartilage. Immunohistochemical (IHC) staining was performed to observe CaMKⅡexpression, and real-time PCR analysis to detect the expression of differentiation and proliferation related genes in condylar cartilages. Results: There was an aberrant chondrocytes differentiation in UAC cartilage. The average thicknesses of condylar cartilage was decreased and SO positive staining area was reduced in UAC group compared with the same period controls and got worse with time. The percentage of CaMKⅡ positive cells was increased. The mRNA expression of differentiation related genes, such as CaMKⅡ and Mmp13, were up-regulated and the proliferation and matrix related genes like Pcna, Col2a1 and Aggrecan mRNA were down-regulated (P<0.05). Conclusion: Differentiation was enhanced and the expression of CaMKⅡ was significantly up-regulated in the degenerative condylar cartilage induced by the aberrant occlusion of UAC.