Karela is a common name of Momordicacharantia. The present study was carried out to study the herb drug interactions between the traditional medicine Karela with Thiazolindinediones, Pioglitazone in normal and diabetic conditions. Blood samples were collected from rats by retro orbital puncture at regular intervals of time 0, 1, 2, 3, 4, 6, 8, 10, 12 hr of rats treated with Pioglitazone 5, 10 and 20mg/kg bd.wt and Momordicacharantia100 and 200mg/kg bd.wt. The Pioglitazone and Karelashoweddose dependent reduction of blood glucose levels. The optimum blood glucose reduction was obtained at 10mg/kg of pioglitazone and 200mg/kg of Karela in normal rats. The blood glucose levels were found to be decreased with corresponding elevated insulin levels in both single and multiple dose combinations of Pioglitazone and Karela in normal rats (4hr) as well as in alloxan induced diabetic rats (4hr) compared with the pioglitazone alone. Since the combination of Karela and pioglitazone produced severe hypoglycemia in combined treatment due to pharmacodynamic interactions, care must be taken while prescribing the combination in clinical situation.