Melatonin, a pineal secretory product, is a potent scavenger of a variety of free radicals. We investigated the role of melatonin on water avoidance stress (WAS)-induced degenerations of the liver parenchyme. Wistar albino rats were exposed to acute WAS (aWAS group) or chronic WAS (cWAS group). Before exposing animals to acute (aWAS + mel group) or chronic WAS (cWAS + mel group), 10 mg/kg melatonin was injected i.p. The liver samples were investigated under light and transmission electron microscope. Malondialdehyde (MDA) and glutathione (GSH) levels were also determined. Prominent vascular congestion and dilated sinusoids, activated Kupffer cells with prominent morphology, dilated granular endoplasmic reticulum membranes, and focal picnotic nuclei were observed in the aWAS group; these morphological changes were severe in the cWAS group. MDA level was increased and GSH level was decreased significantly in the cWAS group. The morphology of liver parenchme in both the aWAS + mel and the cWAS + mel group showed that melatonin significantly reduced the degeneration in liver; besides, a significant decrease in MDA and an increase in GSH levels were observed in the cWAS + mel group. Based on the results, melatonin treatment significantly prevented WAS-induced morphological and biochemical changes in liver parenchyma.