Sulfonamides are widely used in food producing animals for prevention of diseases.Improper use or improper withdraw time will lead to the presence of sulfonamide residues in milk.Many countries have established maximum allowable residue limits (MRLs) for sulfonamides in milk.A method of solid-phase extraction with ODS sorbent on-line to high-performance liquid chromatography for simultaneous determination of 17 sulfonamide residues (sulfaguanidine, sulfanilamide, sulfacetamide, sulfadiazine, sulfathiazole, sulfamerazine, sulfamethazine, sulfamethizole, sulfamonomethoxine, sulfachloropyridazine, sulfadoxine, sulfamethoxazole, sulfisoxazole, sulfadimethoxine, sulfameter, and sulfaquinoxaline) was developed and applied to the sulfonamide resides in milk.The results show the enrichment factors are greater than 30 fold, compared with direct HPLC determination, and the detection limits in sub-g L-1 levels for all 17 sulfonamides.The method applied to the milk sample and the results are reported.