This study aims to explore the effect of selenium in fluoride-induced renal cell apoptosis in rats and determine the optimal level of selenium in drinking water to prevent fluorosis. Experimental animals were divided into a control group, a sodium fluoride-treated group (NaF, 50 mg/L), three sodium selenite-treated groups (Na2SeO3, 0.375, 0.75, and 1.5 mg/L), and three selenium + NaF-treated groups (Na2SeO3, 0.375, 0.75, and 1.5 mg/L; NaF, 50 mg/L). Ultrastructural changes in the kidney tissues of each group were observed by transmission electron microscopy. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and the expressions of Bcl-2 and Bax proteins were detected by immunohistochemical methods. The expressions of Bcl-2 and Bax mRNA were detected by reverse transcription-polymerase chain reaction. The results showed that Bcl-2, Bax, and Bax/Bcl-2 protein expressions in the fluoride and high selenium groups were highly elevated compared with the control group (P < 0.01). Bax expression in the low selenium group and Bcl-2, Bax, and Bax/Bcl-2 protein expressions in the moderate selenium groups were observably elevated (P < 0.05). Bax and Bax/Bcl-2 expressions in the fluoride group and Bax mRNA expression in the high selenium group were highly elevated (P < 0.01). Bax/Bcl-2 mRNA expression in the high selenium group was also highly elevated (P < 0.05). Compared with the fluoride group, the group treated with low selenium has Bax protein expression that was observably reduced (P < 0.05); the group treated with moderate selenium has Bcl-2 protein expression that was observably elevated (P < 0.05), Bax protein expression that was highly reduced (P < 0.01), and Bax/Bcl-2 protein expression that was observably reduced (P < 0.05); the group treated with high selenium has Bcl-2 protein expression that was highly elevated (P < 0.01), Bax protein expression that was highly elevated (P < 0.01), and Bax/Bcl-2 protein expression that was highly reduced (P < 0.01); the groups treated with moderate selenium and high selenium have Bax mRNA expression that was highly reduced (P < 0.01), and the groups treated with high selenium have Bax/Bcl-2 mRNA expression that was observably reduced (P < 0.05). Selenium may inhibit the apoptosis of renal cells in fluorosis rats by regulating the expressions of Bcl-2 and Bax. The optimal dose of Na2SeO3 to protect against fluoride-induced renal cell apoptosis was determined to be 1.5 mg/L.