Thiodiglycolic acid was refluxed with excess methanol or ethanol to obtain dimethyl thiodiglycolate (Ia) or diethyl thiodiglycolate (Ib) using stannous chloride as catalyst. The optimum conditions were SnCl2)=4.0％ and reflux time 3 h, and their yields were 93.5% or 96.4%, respectively. Compound Ia or Ib reacted with glyoxal trimer dehydrate to give thiophene-2, 5-dicarboxylic acid through condensation and hydrolyzation in the presence of potassium hydroxide. The optimal reaction conditions were n (dimethyl thiodiglycolate or diethyl thiodiglycolate) : n (glyoxal trimer dehydrate) : n (potassium hydroxide)＝1: 0.4: 4.4 and reflux time 5 h in cyclohexane. The yields of thiophene-2, 5-dicarboxylic acid were 89.3%~90.0%.