We have investigated the role of cyclooxygenase-2 (COX-2) in myocardial infarction (MI) and ischaemia in rabbits subjected to isoprenaline (ISP) a potent beta-adrenergic agonist. The acute phases of MI and repair mimicked those which occurred in humans. MI after induction with ISP was monitored by following increases seen in the levels of serum enzymes, Troponin I and Creatinine phosphokinase (CPK) in rabbits before and after ISP induced MI. Electrocardiographic (ECG) changes showed typical ST elevation and q-wave development. Histochemical studies of the rabbit heart on 2nd day after ISP injection showed changes of coagulation necrosis. Day 4 total coagulation with the loss of nuclear and striation associated with heavy interstitial infiltrate of neutrophils was found. Day 8 after infarction showed collagen deposition with capillary channels in between the remaining islands of myocytes in the infarcted area on the 16th day scarring was complete. Coronary perfusion rates (CPR) of the infarcted and nimesulide (a COX-2 inhibitor) treated rabbits displayed significant improvement on each corresponding day after infarction as compared to the infarcted and saline treated rabbits (P<0.01). These results suggest that nimesulide, a COX-2 inhibitor exhibit cardioprotective effects in MI.