Thiazolidinediones are commonly used anti-diabetic drugs. Owing to the anti-inflammatory action of TZDs as a result of there action on the PPAR gamma receptor and a proposed action on the prostaglandins, these drugs can be tried in the acute exacerbations of COPD that are also commonly found among diabetic patients. An experimental study of one week was carried out at animal house of Army Medical College, Rawalpindi on a total of 50 guinea pigs (both male and female) of Dunkin Hartley variety, weighing 500 to 600 grams. An isometric volume transducer was used to measure the histamine induced contractions of the smooth muscles. In the similar way contractions with pioglitazone in the presense of histamine, contractions with indomethacin which is a prostaglandin antagonist, in the presence of histamine and mixed effect of pioglitazone along with indomethacin in the presence of histamine was evaluated. Pioglitazone produced significant reduction in histamine-induced contractions of the normal tracheal muscle strips thus identifying its relaxant effect on the tracheal smooth muscles. The contractions of the tracheal muscles were increased when indomethacin was used. The pioglitazone induced relaxation was also reduced in the group pre-treated with indomethacin, thus suggesting an identifiable role of prostaglandins in the relaxant effect of TZDs on the smooth muscles