OBJECTIVE: Test the effect of inhibition of thromboxane synthase versus inhibition of cyclooxygenase (COX) 1,2 on pulmonary gas exchange and heart function during simulated pulmonary embolism (PE) in the rat. METHODS: PE was induced in rats via intrajugular injection of polystyrene microspheres (25 µm). Rats were randomized to one of three posttreatments, 1. Placebo (saline), 2. Thromboxane synthase inhibition (furegrelate sodium), or 3. COX 1,2 inhibition (ketorolac tromethamine). Control rats received no PE. RESULTS: Compared with controls, placebo rats had increased thromboxane B₂ (TxB₂) in bronchalveolar lavage fluid, and increased urinary dinor thromboxane B₂. Furegrelate and ketorolac treatments reduced TxB₂ and dinor thromboxane B₂ to control levels or lower. Both treatments significantly decreased the alveolar deadspace fraction but neither treatment altered arterial oxygenation compared with placebo. Ketorolac increased in-vivo MAP, and ex-vivo LVP and RVP. Furegrelate improved RVP but not LVP. CONCLUSIONS: Experimental PE increased lung and systemic production of thromboxane B₂. Inhibition at the COX 1,2 enzyme was equally effective as inhibition of thromboxane synthase on reducing alveolar deadspace and improving heart function after PE.