Abstract: Objective To investigate the expression of nicotinic acety lcholine receptors(nAChRs)and ERK 1/2 path way in the brain of rat with chronic fluorosis.Methods The SD rats were fed with different concen trations of fluoride (NaF) for six months to establish ratmodel with fluorosis.The prote in levels of nAChRα7 subunit,extracellular signal-reg ulated prote in kinase(ERK 1/2)in ratbrain were detected with Western-blotting and the mRNA level with quantitative real tmie PCR.Results Compared to the control,in the rats treated with high concentrations of fluoride,the protein levels of nAChRα7 were significantly decrea sed(control: 100%±11.5%;lower concentration group:45.2%±9.2%,higher con centration group:29.6%±7.6%).Increased expression of phospho-ERK 1/2 and total ERK 1/2 at prote in level were ob served(control: 100.0%±9.6% and 100.0%±11.7%,lower concentration group:125.4%±9.6% and 132.9%±2.1%,higher concentration group:175.3%±12.4 and 207.4%±7.4%).However,the activation rate of ERK 1/2 was lower in the brain of rats with fluorosis(control: 100.0%±12.2%;lower concentration group:82.919%±4.9%;higher concentration group:65.9%±3.7%).There was no difference of nAChRα7 subunit and ERK 1/2 at mRNA level between the rats with fluorosis and controls.The decreased expression in nAChRα7 subunit had a correlation with the activation rate of ERK 1/2(r=0.696,P < 0.05).Conclusion The changed ERK 1/2 in brain induced by chronic fluorosis mightbe con nected with the depressed expression of nAChRα7.