In the present study, we aimed to assess the anti-inflammatory effect of calcium carbonate, diltiazem and their combination with aspirin as well as the possible underlying mechanism. Calcium carbonate (10 and 50 mg/kg), diltiazem (4mg/kg) and aspirin (54 and 200 mg/kg) were administered orally in different groups of rats to study their effect on acute inflammation induced by yeast. Two animal models of acute inflammation were used; rat paw edema and rat air pouch model. The effect of the aforementioned drugs on paw volume, total leucocytic count, and intereukin-6 (IL-6) level in air pouch exudates were studied.In the present study both calcium carbonate (50mg/kg) and diltiazem (4mg/kg) produced significant reduction in paw edema volume by 65.2% and 50 % respectively. In the air pouch exudates, calcium carbonate (50mg/kg) and diltiazem (4mg/kg) significantly reduced the total leucocytic count (by 52% & 53.4% respectively) and IL 6 level (by 37.6% & 35.2% respectively). We found that neither calcium carbonate in the dose of 10 mg/kg nor aspirin (54mg/kg) has any anti-inflammatory effect. However, when combined with each other they produced significant reduction in paw edema volume by 73.1%. In the air pouch exudates, the same combination significantly reduced the total leucocytic count (by 50.7%) and IL 6 (by 55.6%). It is to be noted that the anti-inflammatory effect of this combination was comparable to that of aspirin (200 mg/kg) in the reduction of paw edema volume and IL 6 level.Similarly, diltiazem (4mg/kg) potentiated the anti-inflammatory activity of aspirin (54mg/kg), as their combination produced significant reduction in paw edema volume by 61.1%, total leucocytic count (by 58.3%) and IL 6 level (by 49.3%). It is to be noted that the anti-inflammatory effect of this combination was comparable to that of aspirin (200 mg/kg). The mechanism of anti-inflammatory action of the tested drugs was explored by observing their effect on oxidative stress as measured by level of malondialdehyde (MDA) in the air pouch exudates.Both calcium carbonate (10 and 50 mg/kg) and diltiazem (4 mg/kg) produced significant reduction in MDA level by 17.8%, 38.1% and 29.4% respectively. When each of calcium carbonate (10 mg/kg) and diltiazem (4 mg/kg) was combined with aspirin (54mg/kg), they produced a more significant reduction in MDA level by 52.3% and 41.6% respectively.We concluded that both calcium carbonate and diltiazem possess anti-inflammatory action that may be mediated via their ability to modulate oxidative stress. Also both of them can potentiate aspirin in its sub-antiinflammatory dose.