Aspirin or ethanol induced gastric ulcer rat models are the most frequently used in studies. Aspirin and ethanol induced gastric ulcers through different pathways involving COX-2 and iNOS. The aim of this study was to examine the expression of COX-2 and iNOS in gastric ulcer rat model induced by ethanol and aspirin. Twenty-one Sprague Dawley rats were divided into 7 groups i.e. control group (CA), ethanol 1 st day (ED 1), ethanol 3 rd day (ED 3), ethanol 5 th day (ED 5), aspirin 4 th day (AD 4), aspirin 6 th day (AD 6), and aspirin 8 th day (AD 8). Oral administration of aspirin was at 200mg/kgBW and the 100% ethanol at 1mL/200gBW. Macroscopic and microscopic observations were done to examine the gastric mucosal damage, COX-2 and iNOS expressions. Severe gastric ulcers were observed in ED 1 and AD 4 groups and mild gastric mucosal damage was observed in ED 3 , ED 5 , AD 6 and AD 8 groups. Microscopically, light erosion was shown by the CA and AD 8 groups. Erosion was also shown by ED 3 , ED 5 , and AD 6 groups. The most severe damage with ulcers and heavier bleeding were shown by the ED 1 and AD 4 groups. Weak COX-2 expression was found in the CA, while the highest COX-2 expression was found in the ED 1. The iNOS expression in the ethanol groups was still increasing until the 5 th day (ED 5). In the aspirin groups, it reached the peak on the 3 rd day (AD 6), and already declined on the 5 th day (AD 8). In conclusion, the damage process of ethanol induced gastric ulcer occurred faster than that by aspirin. The highest COX-2 expression in the ethanol and aspirin groups were shown at the onset begin. iNOS expression in ethanol induced ulcer groups still increased until the 5 th day, while in the aspirin induced ulcer groups already declined in the 5 th day. ABSTRAK Tikus model ulkus lambung yang diinduksi oleh aspirin atau etanol adalah model yang paling sering digunakan dalam penelitian. Ulkus lambung yang diinduksi aspirin mempunyai jalur pathogenesis yang berbeda dengan yang diinduksi oleh etanol, namun keduanya melibatkan COX-2 dan iNOS. Tujuan penelitian ini adalah mengkaji ekspresi COX-2 dan iNOS pada tikus model ulkus lambung yang diinduksi oleh ethanol dan aspirin. Dua puluh satu tikus Sprague Dawley dibagi menjadi 7 yaitu kelompok kontrol (CA), etanol hari pertama (ED 1), etanol hari ketiga (ED 3), etanol hari kelima (ED 5), aspirin hari keempat (AD 4), aspirin hari keenam (AD 6), dan aspirin hari kedelapan (AD 8). Perlakuan diberikan secara oral, dengan dosis aspirin sebesar 200 mg/kgBB dan dosis 100% etanol sebesar 1mL/200gBB. Pengamatan makroskopis dan mikroskopis dilakukan untuk menilai kerusakan mukosa lambung, ekspresi COX-2 dan iNOS. Ulkus lambung berat terlihat pada kelompok ED 1 dan AD 4 dan kerusakan mukosa lambung ringan terlihat pada kelompok ED 3 , ED 5 , AD 6 and AD 8. Secara mikroskopis, erosi ringan terlihat pada kelompok CA dan AD 8. Erosi juga terlihat kelompok ED 3 , ED 5 , dan AD 6. Kerusakan paling berat dengan ulkus dan pendarahan terlihat pada kelompok ED 1 dan AD 4. Ekspresi COX-2 le...