Recent evidence has demonstrated that simultaneous activation of PPAR isoforms and inhibition of (+)-JQ1 Epigenetic Reader Domain inhibitor cyclooxygenase-2 may be a good approach to treat inflammatory diseases and cancer. Despite the use of PPAR agonists in a diversity of inflammatory disorders, only little evidence has associated PPAR activation by thiazolidine molecules, such as pioglitazone and rosiglitazone, with the control and healing of gastric tissue damage. Lesions caused by ischemia/reperfusion or NSAID intake were reduced in rats pre-treated with a PPAR�� agonist, and the beneficial effect was correlated to reduced mRNA levels and protein content of proinflammatory cytokines and enzymes, such as COX-2, iNOS, and oxidative enzymes, as well as overexpression of plateletendothelial cell adhesion molecule and heat-shock protein 70 in injured gastric tissue. More recently, it has been shown that rosiglitazone prevents indomethacin-induced gastric ulcers in type II diabetic rats. Here, we investigated the efficacy and mechanisms of action of an indole-thiazolidine molecule designed to be a PPAR panagonist and COX inhibitor, named LYSO-7, on Et/HClinduced gastric lesions in mice. LY2835219 LYSO-7 provided cytoprotection by impairing neutrophil influx and reestablishing the vascular network. The latter effect was mediated by the in vivo balance of iNOS/eNOS protein expression. To our knowledge, the proposed mechanism of a PPAR pan-agonist molecule has not been previously demonstrated in vivo in an Et/HCl model, and points out the use of PPAR pan-agonists as a possible therapeutic approach for acute gastric lesions. The effectiveness of preventive and therapeutic approaches for gastric ulcers has been limited to one pathway, i.e. proton pump inhibition, and the adverse effects of drugs. Using an acute experimental model of gastric lesions, we show here that a indole-thiazolidine molecule, a PPAR pan-agonist and COX inhibitor named LYSO-7, does not affect gastric secretion, but causes cytoprotection by inhibiting neutrophil influx into the injured area and by maintaining blood flow in the gastric microcirculatory network. The latter effect is mediated by NO, which seems to be produced by eNOS. The thiazolidine-2,4-dione region of the thiazolidione molecule binds to the retinoid X receptor coupled to PPARs to form heterodimeric complexes, which then bind to the peroxisome proliferator response element gene promoter, leading to the regulation of gene transcription. Although LYSO-7 maintains the thiazolidine-2,4-dione group, it is an indole-substituted properly synthesized to also display inhibitory activity against COX. In vitro studies had already shown the PPAR pan-agonist activity of LYSO-7, and here we confirm that the activity is maintained in vivo, as levels of PPAR�� gene and protein expression were enhanced by LYSO-7 treatment.