Endoscopic submucosal dissection (ESD) is a minimally invasive technique allowing for the removal of early gastrointestinal (GI) tumors, widely considered as a valid alternative to conventional surgery. However, ESD is technically demanding, and potentially severe complications, such as bleeding and perforation, may occur. Energy-based techniques (e.g., radiofrequency ablation) might offer a potential alternative to ESD. However, their use mandates the ability to predict the damage induced and to identify a "signature" of the complete ablation, without the need for a physical specimen. Ideally, an energy-based procedure should be tunable in order to limit the ablation to the superficial layers, namely mucosa (M) and submucosa (SM), without injuring the muscularis propria (MP), thereby minimizing GI perforation. This experimental study aims to investigate thermal damage induced by Nd:YAG laser on the gastric wall, at different laser settings such as power (P) and time (t). Laser ablation was performed on the stomach wall of 6 Wistar rats. Two powers (2.5W and 1.0W) and 3 exposure times (12s, 6s and 2s) were tested, for a total of 30 ablations. Histological analysis allowed to assess thermal damage, in terms of damage depth (DD) and identification of involved layers. The ratio (R) between DD and the total depth (TD) of target layers (M+SM) was used as an index to evaluate the effectiveness of laser settings. At P=2.5W, MP was damaged (R>1) in the majority of cases (11/15). At P=1.0W, MP was preserved in all tests (R<;1), and rarely (4/15) did the damage reach the whole SM (R=1). Histopathological analysis evidenced that tissue damage was strongly related to the variable tissue thickness. These preliminary results seem to support the fact that endoscopic tunable laser ablation is feasible with a consistent damage/power correlation. Further tests are required to optimize the settings for applications on early GI tumors.