To investigate the effect of excessive fluoride ingestion (EFI) on the differential expression of collagen phenotypes and chondrocyte differentiation in cartilage, 60 Sprague-Dawley rats, 4-6 weeks old, were divided into three groups and exposed to O (control), 50, and 100 ppm fluoride (from NaF) in drinking water for 3 to 5 months. Correlating with the increased F in the serum and bone in the two groups exposed to EFI, chondrocytes in the proliferative and hypertrophic zones of growth plate cartilage (GPC) and rib cartilage (RC) were retained and formed a mixture tissue of cartilage peninsulas or islands with ossified islands in the deep zone of GPC and RC. Staining reactions for types II and X collagen were increased in the over-thickened region of GPC and were decreased in RC. Type X collagen staining reactions were also increased in the upper and middle zones in articular cartilage (AC) of tibia in the higher fluoride (EFI-II) group. Abnormal collagen expression in rats of the EFI groups resulted from abnormal differentiation of chondrocytes in proliferative and hypertrophic zones in GPC and RC and from degenerative changes in AC of rats in the EFI groups. Four types of abnormal chondrocyte differentiation in hyaline cartilage of rats with skeletal fluorosis (SF) suggested two pathogenic mechanisms for early stage of SF: osteomalacia-like changes in GPC and RC coupled with delayed mineralization and degenerative changes in AC.