Background: – This study intends to address the scarcity of data regarding the pathogenesis of Baclofen poisoning in humans, which has seen a recent increase, worldwide, especially amongst the young people. Another reason for the conduction of this study was lack of the substantial data about the histo-pathological findings of lungs, in synergistic toxicity of Baclofen with Ethanol, in-spite of it being very common in humans, and both being respiratory depressant with similar mechanism of action. Purpose: – The authors aimed to understand the pathogenesis of fatal poisonings in humans due to Baclofen in combination with Ethanol via an animal research model. The enhancement of the overall scientific literature by extending research along the lines of the handful studies available in this regard was another adjunct goal of the study. Material and methods: Fifteen Wistar rats were divided into control and test group of five and ten subjects respectively. The test group was further divided into two sub-groups of five each, with Baclofen administered to one, and it in conjunction with Ethanol to the other, in lowest dosages adjusted for the humans. Rats in both the groups were euthanized by dislocation of the cervical vertebrae for the histopathology examination. Results: Capillary and venous plethora, hemorrhages in the inter-alveolar septi, hemorrhages into the alveoli and sludging was seen in the 1st sub-group. The plethora of venules, capillaries and arterioles, with sludging by the WBC (white blood corpuscle) infiltrates was seen in the 2nd sub-group. Desquamation of the ciliated epithelium and edematous thickening of the intra-alveolar septi, along with features suggestive of the peri-vascular edema was seen in the 2nd sub-group. The morphometric analysis of the micro vessels showed a significantly higher value of the arteriolar diameter in the 2nd sub-group, in comparison to 1st, but the venular diameter in the two sub-groups did not differ to any extent. © 2022 Elsevier Ltd and Faculty of Forensic and Legal Medicine