Objective To explore the chronic effects of mild and moderate iodine excess and iodine restriction on apoptosis of thyrocytes. Methods Wistar rats were exposed to 4 different doses of iodine: 4 μg/d (control), 6 μg/d (1.5 fold iodine excess), 12 μg/d (3 fold iodine excess), and 24 μg/d (6 fold iodine excess) for 1, 2, 4 and 8 months. Some rats treated for 8 months were fed with 4 μg/d iodine for another 3 months. Urinary iodine concentration was monitored by arscnic/cerium catalyzing spectrophotography. Apoptosis was determined by flow cytometry after Annexin V-FTTC staining and uhrastructure assessment under electronic microscope. Cell cycle kinetics was analyzed by flow eytometry after propidium iodine staining. Fluorescent measurement by DCFH-DA probe was used to determine the intracellular reactive oxygen species (ROS) level. Expressions of apoptic proteins were analyzed by flow cytometry and immunohistochemistry. Results Apoptotosis rate and ROS production in thyrocytes were significantly increased in 3 and 6 fold iodine excess groups after 4 months and 8 months (all P < 0.05), which was reversed with iodine restriction. 6 fold iodine exposure was proved to cause a reduction of cells in GOG1-phase (64% and 67% vs 80%, both P < 0. 05) and a concomitant accumulation in S-phase (5% and 6% vs 3%, both P <0.05) after 4 months and 8 months. Expressions of Fas, FasL and TRAIL proteins in 3 and 6 fold iodine excess groups after 8 months were increased by 2 to 4 times compared with control group and did not return to normal after iodine restriction. Bcl-2 and Bax remained constant. Positive correlations were observed among iodine amount, apoptosis rate and ROS level in 6 fold iodine excess group after 8 months (r = 0. 637-0.790, P < 0.01). Conclusion Chronic iodine excess results in thyrocyte apoptosis due probably to generation of ROS.