Abstract: To explore the relationship between methylation capacity and skin lesions among the patients chronically exposed to arsenic through drinking water.Methods Patients with arsenic related skin lesions were graded according to the Chinese Standard of Diagnosis for Endemic Arsenicosis.Levels of inorganic arsenic(iAs),monomethylated arsenic(MMA),dimethylated arsenic(DMA)in blood were detected by atomic absorption spectrophotometer with an arsenic speciation pretreatment system.iAs%,MMA%,and DMA% were calculated.Total arsenic(tAs),the first methylation ratio(FMR)and the second methylation ratio(SMR)were calculated as iAs+MMA+DMA,(MMA+DMA)/tAs and DMA/(MMA+DMA),respectively.Results There were no significant gender differences in the level of iAs,MMA,DMA,tAs,iAs%,MMA%,DMA%,FMR,and SMR.No significant difference in FMR was found among the mild,moderate and advanced group of skin lesions.SMR of moderate and advanced group(0.36±0.11, 0.37±0.08)were markedly lower than that of mild(0.48±0.11),while MMA% of moderate and advanced group(0.50±0.06,0.52±0.03)was significantly higher than that of mild(0.41±0.09).Significant negative correlation was found between SMR and the grade of skin lesions(r=-0.429,P<0.05).Conclusion The results suggest that lowsecondary arsenic methylation capacity and high MMA proportion are associated with the severity of arsenic-related skin lesion.