Abstract： Objective To investigate the effects of fluoride on Fas expression, caspase-3 and caspase-8 activity and apoptosis in rat incisor cells. Methods Forty male SD rats were divided into 4 groups randomly and provided with distilled water containing NaF at the doses of 0, 10, 50 and 100 mg/L respectively. Each group had 10 animals. Five animals were sacrificed at 60 and 90 days respectively. Fas expression was measured with immunohistochemistry, and colorimetric assay was used to examine caspase-3 and caspase-8 activity with enzyme-labelled meter. The apoptosis was detected by flow cytometry in mandibular incisor cells. Results NaF at the doses of 10,50 and 100 mg/L for 60 d and 90 d caused Fas overexpression, promoted activity of caspase-3 and caspase-8, increased apoptosis rate in mandibular incisor cells. At 60 days,the value of Fas expression was 0.1819±0.0025 for control, 0.2120±0.0084 for 10 mg/L NaF group, 0.2283±0.0183 for 50 mg/L NaF group, 0.2818±0.0233 for 100 mg/L NaF group. At 90 days,the value of Fas expression was 0.2077±0.0289 for control, 0.2216±0.0105 for 10 mg/L NaF group, 0.2377±0.0059 for 50 mg/L NaF group, 0.2775±0.0088 for 100 mg/L NaF group. Statistics analysis yielded close relationship between the dose of NaF in water and the Fas expression, and also between the dose of NaF in water and caspase-3 activities, and the relative coefficient was 0.9728(60 d, P<0.01) and 0.9889(90 d, P<0.01)for Fas expression, 0.9533(60 d, P<0.01)and 0.9849(90 d, P<0.01)for caspase-3 activity respectively. Apoptosis rate and caspase-8 activity also had close relationship with the NaF doses, and the relative coefficient was 0.9733(90 d,P<0.01)for apoptosis, 0.9928(90 d, P<0.01)for caspase-8. At the doses of 10, 50 and 100 mg/L NaF for 60 d and 90 d, obvious relationship was found between Fas expression and caspase-3 activity, and the relative coefficient was 0.9619(60 d, P<0.01) and 0.9912(90 d, P<0.01). Obvious relationship between Fas expression and apoptosis, between Fas expression and caspase-8 activity was found in groups for 90 d, and the relative coefficient was 0.9841(P<0.01)for apoptosis, 0.9767(P<0.01)for caspase-8. Conclusions Fluoride could induce Fas overexpression and mediate caspase activation and apoptosis at the doses of 10,50 and 100 mg/L for 60 d and 90 d in rat mandibular incisor cells.